Trial Outcomes & Findings for A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis (NCT NCT04033445)

Last Updated: 2025-11-12

Results Overview

Clinical response was defined as a decrease from induction baseline in the modified Mayo score by greater than or equal to (\>=) 30 percent (%) and \>=2 points, with either a \>=1 point decrease from baseline (Week 0 of IS-1) in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. This outcome measure was planned to be analyzed for specified arms only.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2/PHASE3

Target enrollment

1064 participants

Primary outcome timeframe

At Week I-12

Results posted on

2025-11-12

Participant Flow

This study consisted of 3 separate studies: induction study 1 (IS-1), induction study 2 (IS-2) and maintenance study (MS). In IS-1 and IS-2, participants with modified Mayo score (MMS) of 4 to 9 at baseline (Induction Week 0 \[Week I-0\]) with inadequate response or failed to tolerate conventional or advanced therapy were enrolled.

IS-1 and IS-2 participants with clinical response (CR) at Week I-12/Week I-24 entered MS. Participants who had no CR at Week I-24 stopped study drug and had safety follow-up up to 12 weeks after last dose. CR: decrease from induction baseline in MMS by greater than or equal to (\>=)30 percent (%) and \>=2 points, with either \>=1 point decrease from baseline in rectal bleeding (RB) subscore/RB subscore of 0 or 1. MMS contained 3 subscores: stool frequency, rectal bleeding and endoscopic subscore.

Participant milestones

Participant milestones
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 Participants who initially received placebo and did not achieve clinical response at IS-1 Period 1 Week I-12 were crossed over to guselkumab and received single dose of guselkumab 200 mg IV infusion and placebo (matching to guselkumab) subcutaneous (SC) injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-1: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 Participants who initially received guselkumab 200 mg or 400 mg IV infusion and did not achieve clinical response at IS-1 Period 1 Week I-12 received single dose of guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 Participants received single dose of placebo (matched to guselkumab) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 200 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 Participants who initially received placebo and did not achieve clinical response at Week I-12 were crossed over to guselkumab and received guselkumab 200 mg IV infusion and placebo (matching to guselkumab) SC injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 Participants who initially received guselkumab 200 mg IV infusion and did not achieve clinical response at Week I-12 received guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	MS: Randomized: Placebo SC Every 4 Weeks (q4w) Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive placebo (matching to guselkumab) SC injection every 4 weeks (q4w) starting from Week M-0 till Week M-40. Participants who met criteria for loss of clinical response ( that is \[i.e.\], no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Randomized: Guselkumab 100 mg SC q8w Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 100 mg SC injection q8w starting from Week M-4 till Week M-36. Participants who met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Randomized: Guselkumab 200 mg SC q4w Participants who achieved clinical response at IS-1or IS-2 Week I-12 (Period 1)(previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40. Participants who met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w (sham dose adjustment) from the time of dose adjustment through maintenance Week 40.	MS: Nonrandomized: Placebo SC q4w Participants who were treated previously with placebo (matched to guselkumab) and achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) entered in MS and received placebo (matched to guselkumab) SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Guselkumab 200 mg SC q4w Participants who were randomized to guselkumab and did not achieve clinical response at IS-1 or IS-2 Week I-12 (period 1) but achieved clinical response at IS-1 or IS-2 Week I-24 (Period 2) entered in MS and received guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.
IS-1 and IS-2 Period 2 (Week 12 to 24) STARTED	0	0	0	67	79	0	0	172	129	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) STARTED	109	108	111	0	0	296	440	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Treated	108	108	111	0	0	295	440	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Full Analysis Set (FAS)	105	101	107	0	0	280	421	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) FAS Participants Who Enrolled Into MS	32	60	65	0	0	82	274	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) COMPLETED	103	105	110	0	0	270	422	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) NOT COMPLETED	6	3	1	0	0	26	18	0	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) IS-1: Period 1 Guselkumab 200 mg IV Non Responders	0	0	0	0	38	0	0	0	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) IS-1: Period 1 Guselkumab 400 mg IV Non Responders	0	0	0	0	41	0	0	0	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Treated	0	0	0	67	79	0	0	171	129	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) FAS Participants Who Enrolled Into MS	0	0	0	49	49	0	0	120	74	0	0	0	0	0
Maintenance Study (Week 0 to Week 44) STARTED	0	0	0	0	0	0	0	0	0	201	199	199	122	125
IS-1 and IS-2 Period 2 (Week 12 to 24) COMPLETED	0	0	0	64	77	0	0	162	117	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) NOT COMPLETED	0	0	0	3	2	0	0	10	12	0	0	0	0	0
Maintenance Study (Week 0 to Week 44) Treated	0	0	0	0	0	0	0	0	0	201	199	199	122	125
Maintenance Study (Week 0 to Week 44) Full Analysis Set	0	0	0	0	0	0	0	0	0	190	188	190	114	123
Maintenance Study (Week 0 to Week 44) Safety All Randomized and Treated Analysis Set	0	0	0	0	0	0	0	0	0	203	197	199	0	0
Maintenance Study (Week 0 to Week 44) COMPLETED	0	0	0	0	0	0	0	0	0	173	177	176	95	107
Maintenance Study (Week 0 to Week 44) Dose Adjustment	0	0	0	0	0	0	0	0	0	75	23	31	0	0
Maintenance Study (Week 0 to Week 44) Safety All Nonrandomized and Treated Analysis Set	0	0	0	0	0	0	0	0	0	0	0	0	122	125
Maintenance Study (Week 0 to Week 44) NOT COMPLETED	0	0	0	0	0	0	0	0	0	28	22	23	27	18

Reasons for withdrawal

Reasons for withdrawal
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 Participants who initially received placebo and did not achieve clinical response at IS-1 Period 1 Week I-12 were crossed over to guselkumab and received single dose of guselkumab 200 mg IV infusion and placebo (matching to guselkumab) subcutaneous (SC) injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-1: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 Participants who initially received guselkumab 200 mg or 400 mg IV infusion and did not achieve clinical response at IS-1 Period 1 Week I-12 received single dose of guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 Participants received single dose of placebo (matched to guselkumab) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 200 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 Participants who initially received placebo and did not achieve clinical response at Week I-12 were crossed over to guselkumab and received guselkumab 200 mg IV infusion and placebo (matching to guselkumab) SC injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 Participants who initially received guselkumab 200 mg IV infusion and did not achieve clinical response at Week I-12 received guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	MS: Randomized: Placebo SC Every 4 Weeks (q4w) Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive placebo (matching to guselkumab) SC injection every 4 weeks (q4w) starting from Week M-0 till Week M-40. Participants who met criteria for loss of clinical response ( that is \[i.e.\], no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Randomized: Guselkumab 100 mg SC q8w Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 100 mg SC injection q8w starting from Week M-4 till Week M-36. Participants who met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Randomized: Guselkumab 200 mg SC q4w Participants who achieved clinical response at IS-1or IS-2 Week I-12 (Period 1)(previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40. Participants who met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w (sham dose adjustment) from the time of dose adjustment through maintenance Week 40.	MS: Nonrandomized: Placebo SC q4w Participants who were treated previously with placebo (matched to guselkumab) and achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) entered in MS and received placebo (matched to guselkumab) SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Guselkumab 200 mg SC q4w Participants who were randomized to guselkumab and did not achieve clinical response at IS-1 or IS-2 Week I-12 (period 1) but achieved clinical response at IS-1 or IS-2 Week I-24 (Period 2) entered in MS and received guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.
IS-1 and IS-2 Period 1 (Week 0 to 12) Adverse Event	2	1	0	0	0	9	7	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Death	0	0	0	0	0	1	1	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Lack of Efficacy	2	0	0	0	0	0	2	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Physician Decision	0	0	0	0	0	2	1	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Pregnancy	0	0	0	0	0	0	1	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Withdrawal by Subject	1	1	1	0	0	12	6	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Other	0	1	0	0	0	1	0	0	0	0	0	0	0	0
IS-1 and IS-2 Period 1 (Week 0 to 12) Randomized but not treated	1	0	0	0	0	1	0	0	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Adverse Event	0	0	0	2	2	0	0	4	6	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Lack of Efficacy	0	0	0	0	0	0	0	1	3	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Lost to Follow-up	0	0	0	0	0	0	0	0	1	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Protocol Violation	0	0	0	1	0	0	0	0	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Withdrawal by Subject	0	0	0	0	0	0	0	3	2	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Other	0	0	0	0	0	0	0	1	0	0	0	0	0	0
IS-1 and IS-2 Period 2 (Week 12 to 24) Crossed over but not treated	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Maintenance Study (Week 0 to Week 44) Adverse Event	0	0	0	0	0	0	0	0	0	12	9	10	11	5
Maintenance Study (Week 0 to Week 44) Lack of Efficacy	0	0	0	0	0	0	0	0	0	6	3	1	5	3
Maintenance Study (Week 0 to Week 44) Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	1	1	0	1
Maintenance Study (Week 0 to Week 44) Physician Decision	0	0	0	0	0	0	0	0	0	0	4	1	2	1
Maintenance Study (Week 0 to Week 44) Withdrawal by Subject	0	0	0	0	0	0	0	0	0	8	4	7	6	5
Maintenance Study (Week 0 to Week 44) Non-Compliance With Study Drug	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Maintenance Study (Week 0 to Week 44) Other	0	0	0	0	0	0	0	0	0	1	1	2	2	2
Maintenance Study (Week 0 to Week 44) Site Closure in Ukraine	0	0	0	0	0	0	0	0	0	1	0	1	1	0

Baseline Characteristics

A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=105 Participants Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=101 Participants Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 n=107 Participants Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-2: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=280 Participants Participants received single dose of placebo (matched to guselkumab) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=421 Participants Participants received single dose of guselkumab 200 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	Total n=1014 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=10 Participants	4 Participants n=10 Participants	5 Participants n=20 Participants	19 Participants n=45 Participants	28 Participants n=44 Participants	60 Participants n=8 Participants
Age, Continuous	41.2 Years STANDARD_DEVIATION 15.05 • n=10 Participants	43.3 Years STANDARD_DEVIATION 14.28 • n=10 Participants	40.4 Years STANDARD_DEVIATION 13.84 • n=20 Participants	39.8 Years STANDARD_DEVIATION 13.43 • n=45 Participants	41 Years STANDARD_DEVIATION 13.9 • n=44 Participants	40.9 Years STANDARD_DEVIATION 13.93 • n=8 Participants
Sex: Female, Male Female	39 Participants n=10 Participants	41 Participants n=10 Participants	48 Participants n=20 Participants	119 Participants n=45 Participants	183 Participants n=44 Participants	430 Participants n=8 Participants
Sex: Female, Male Male	66 Participants n=10 Participants	60 Participants n=10 Participants	59 Participants n=20 Participants	161 Participants n=45 Participants	238 Participants n=44 Participants	584 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=10 Participants	5 Participants n=10 Participants	4 Participants n=20 Participants	21 Participants n=45 Participants	25 Participants n=44 Participants	59 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	97 Participants n=10 Participants	92 Participants n=10 Participants	98 Participants n=20 Participants	240 Participants n=45 Participants	368 Participants n=44 Participants	895 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	24 Participants n=10 Participants	23 Participants n=10 Participants	27 Participants n=20 Participants	62 Participants n=45 Participants	88 Participants n=44 Participants	224 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	1 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	3 Participants n=45 Participants	4 Participants n=44 Participants	10 Participants n=8 Participants
Race (NIH/OMB) White	77 Participants n=10 Participants	73 Participants n=10 Participants	74 Participants n=20 Participants	205 Participants n=45 Participants	304 Participants n=44 Participants	733 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants	2 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=10 Participants	3 Participants n=10 Participants	5 Participants n=20 Participants	10 Participants n=45 Participants	22 Participants n=44 Participants	43 Participants n=8 Participants
Region of Enrollment Argentina	0 Participants n=10 Participants	0 Participants n=10 Participants	2 Participants n=20 Participants	5 Participants n=45 Participants	10 Participants n=44 Participants	17 Participants n=8 Participants
Region of Enrollment Australia	2 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants	7 Participants n=45 Participants	14 Participants n=44 Participants	26 Participants n=8 Participants
Region of Enrollment Belgium	1 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants	3 Participants n=44 Participants	7 Participants n=8 Participants
Region of Enrollment Brazil	0 Participants n=10 Participants	2 Participants n=10 Participants	0 Participants n=20 Participants	12 Participants n=45 Participants	15 Participants n=44 Participants	29 Participants n=8 Participants
Region of Enrollment Bulgaria	1 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants	3 Participants n=44 Participants	7 Participants n=8 Participants
Region of Enrollment Canada	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	2 Participants n=45 Participants	5 Participants n=44 Participants	7 Participants n=8 Participants
Region of Enrollment China	7 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	26 Participants n=45 Participants	35 Participants n=44 Participants	72 Participants n=8 Participants
Region of Enrollment Czech Republic	1 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	11 Participants n=45 Participants	17 Participants n=44 Participants	32 Participants n=8 Participants
Region of Enrollment France	5 Participants n=10 Participants	10 Participants n=10 Participants	6 Participants n=20 Participants	10 Participants n=45 Participants	30 Participants n=44 Participants	61 Participants n=8 Participants
Region of Enrollment Germany	3 Participants n=10 Participants	3 Participants n=10 Participants	3 Participants n=20 Participants	11 Participants n=45 Participants	8 Participants n=44 Participants	28 Participants n=8 Participants
Region of Enrollment Hungary	4 Participants n=10 Participants	5 Participants n=10 Participants	3 Participants n=20 Participants	11 Participants n=45 Participants	17 Participants n=44 Participants	40 Participants n=8 Participants
Region of Enrollment Ireland	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	1 Participants n=45 Participants	0 Participants n=44 Participants	1 Participants n=8 Participants
Region of Enrollment Israel	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	5 Participants n=45 Participants	7 Participants n=44 Participants	14 Participants n=8 Participants
Region of Enrollment Italy	5 Participants n=10 Participants	2 Participants n=10 Participants	6 Participants n=20 Participants	14 Participants n=45 Participants	15 Participants n=44 Participants	42 Participants n=8 Participants
Region of Enrollment Japan	9 Participants n=10 Participants	12 Participants n=10 Participants	15 Participants n=20 Participants	25 Participants n=45 Participants	33 Participants n=44 Participants	94 Participants n=8 Participants
Region of Enrollment Jordan	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	16 Participants n=45 Participants	18 Participants n=44 Participants	34 Participants n=8 Participants
Region of Enrollment Latvia	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	5 Participants n=45 Participants	3 Participants n=44 Participants	8 Participants n=8 Participants
Region of Enrollment Malaysia	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants	4 Participants n=44 Participants	7 Participants n=8 Participants
Region of Enrollment New Zealand	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants	5 Participants n=44 Participants	8 Participants n=8 Participants
Region of Enrollment Poland	19 Participants n=10 Participants	22 Participants n=10 Participants	24 Participants n=20 Participants	47 Participants n=45 Participants	71 Participants n=44 Participants	183 Participants n=8 Participants
Region of Enrollment Portugal	2 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	1 Participants n=45 Participants	0 Participants n=44 Participants	6 Participants n=8 Participants
Region of Enrollment Russian Federation	9 Participants n=10 Participants	7 Participants n=10 Participants	6 Participants n=20 Participants	18 Participants n=45 Participants	20 Participants n=44 Participants	60 Participants n=8 Participants
Region of Enrollment Serbia	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	5 Participants n=45 Participants	5 Participants n=44 Participants	10 Participants n=8 Participants
Region of Enrollment Slovakia	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	2 Participants n=45 Participants	12 Participants n=44 Participants	14 Participants n=8 Participants
Region of Enrollment South Korea	6 Participants n=10 Participants	7 Participants n=10 Participants	5 Participants n=20 Participants	2 Participants n=45 Participants	11 Participants n=44 Participants	31 Participants n=8 Participants
Region of Enrollment Spain	2 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants	2 Participants n=44 Participants	8 Participants n=8 Participants
Region of Enrollment Sweden	2 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants	6 Participants n=8 Participants
Region of Enrollment Taiwan	2 Participants n=10 Participants	1 Participants n=10 Participants	3 Participants n=20 Participants	2 Participants n=45 Participants	1 Participants n=44 Participants	9 Participants n=8 Participants
Region of Enrollment Turkey	0 Participants n=10 Participants	0 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants	11 Participants n=44 Participants	16 Participants n=8 Participants
Region of Enrollment Ukraine	16 Participants n=10 Participants	16 Participants n=10 Participants	14 Participants n=20 Participants	13 Participants n=45 Participants	20 Participants n=44 Participants	79 Participants n=8 Participants
Region of Enrollment United Kingdom	3 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	3 Participants n=45 Participants	6 Participants n=44 Participants	14 Participants n=8 Participants
Region of Enrollment United States	6 Participants n=10 Participants	3 Participants n=10 Participants	7 Participants n=20 Participants	11 Participants n=45 Participants	17 Participants n=44 Participants	44 Participants n=8 Participants

PRIMARY outcome

Timeframe: At Week I-12

Population: FAS: all randomized participants (in IS-1) with a modified Mayo score of 5 to 9 who received at least 1 (partial or complete) dose of study intervention.

Outcome measures

Outcome measures
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=105 Participants Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=101 Participants Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 n=107 Participants Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.
Induction Study 1: Percentage of Participants With Clinical Response at Week I-12	27.6 Percentage of participants	61.4 Percentage of participants	60.7 Percentage of participants

PRIMARY outcome

Timeframe: At Week I-12

Population: Full analysis set included all randomized participants (in IS-2) with a modified Mayo score of 5 to 9 who received at least 1 (partial or complete) dose of study intervention.

Clinical remission was based on the modified Mayo score. Clinical remission was defined as Mayo stool frequency subscore of 0 or 1 and not increased from baseline (Week 0 of IS-2), a Mayo rectal bleeding subscore of 0, and Mayo endoscopic subscore of 0 or 1 with no friability. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. This outcome measure was planned to be analyzed for specified arms only.

Outcome measures

Outcome measures
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=280 Participants Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=421 Participants Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.
Induction Study 2: Percentage of Participants With Clinical Remission at Week I-12	7.9 Percentage of participants Interval 4.7 to 11.0	22.6 Percentage of participants Interval 18.6 to 26.6	—

PRIMARY outcome

Timeframe: At Week M-44

Population: Randomized full analysis set included all participants with a modified Mayo score of 5 to 9 who were randomized and received at least 1 (partial or complete) dose of study intervention in the maintenance study.

Clinical remission was based on the modified Mayo score. Clinical remission was defined as Mayo stool frequency subscore of 0 or 1 and not increased from baseline (Week 0 of IS-1 and IS-2), a Mayo rectal bleeding subscore of 0, and Mayo endoscopic subscore of 0 or 1 with no friability. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. This outcome measure was planned to be analyzed for randomized arms only.

Outcome measures

Outcome measures
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=190 Participants Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=188 Participants Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 n=190 Participants Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.
Maintenance Study: Percentage of Participants With Clinical Remission at Week M-44	18.9 Percentage of participants Interval 13.4 to 24.5	45.2 Percentage of participants Interval 38.1 to 52.3	50.0 Percentage of participants Interval 42.9 to 57.1

Deaths: 0 deaths

MS: Dose Adjustment: Guselkumab 200 mg SC q4w to Guselkumab 200 mg SC q4w

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=108 participants at risk Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=108 participants at risk Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 n=111 participants at risk Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 n=67 participants at risk Participants who initially received placebo and did not achieve clinical response at IS-1 Period 1 Week I-12 were crossed over to guselkumab and received single dose of guselkumab 200 mg IV infusion and placebo (matching to guselkumab) subcutaneous (SC) injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-1: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 n=79 participants at risk Participants who initially received guselkumab 200 mg or 400 mg IV infusion and did not achieve clinical response at IS-1 Period 1 Week I-12 received single dose of guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=295 participants at risk Participants received single dose of placebo (matched to guselkumab) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=440 participants at risk Participants received single dose of guselkumab 200 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 n=171 participants at risk Participants who initially received placebo and did not achieve clinical response at Week I-12 were crossed over to guselkumab and received guselkumab 200 mg IV infusion and placebo (matching to guselkumab) SC injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 n=129 participants at risk Participants who initially received guselkumab 200 mg IV infusion and did not achieve clinical response at Week I-12 received guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	MS: Randomized: Placebo SC Every 4 Weeks (q4w) n=203 participants at risk Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive placebo (matching to guselkumab) SC injection every 4 weeks (q4w) starting from Week M-0 till Week M-40.	MS: Randomized: Guselkumab 100 mg SC q8w n=197 participants at risk Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 100 mg SC injection q8w starting from Week M-4 till Week M-36.	MS: Randomized: Guselkumab 200 mg SC q4w n=199 participants at risk Participants who achieved clinical response at IS-1or IS-2 Week I-12 (Period 1)(previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Placebo SC q4w n=122 participants at risk Participants who were treated previously with placebo (matched to guselkumab) and achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) entered in MS and received placebo (matched to guselkumab) SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Guselkumab 200 mg SC q4w n=125 participants at risk Participants who were randomized to guselkumab and did not achieve clinical response at IS-1 or IS-2 Week I-12 (period 1) but achieved clinical response at IS-1 or IS-2 Week I-24 (Period 2) entered in MS and received guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.	MS: Dose Adjustment: Placebo SC q4w to Guselkumab 200 mg SC q4w n=75 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive placebo (matched to guselkumab) SC injection and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Dose Adjustment: Guselkumab 100 mg SC q8w to Guselkumab 200 mg SC q4w n=23 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive guselkumab 100 mg SC injection q4w and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Dose Adjustment: Guselkumab 200 mg SC q4w to Guselkumab 200 mg SC q4w n=31 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive guselkumab 200 mg SC injection q4w and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w (sham dose adjustment) from the time of dose adjustment through maintenance Week 40.
Blood and lymphatic system disorders Anaemia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Cardiac disorders Atrial Fibrillation	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Cardiac disorders Cardiac Arrest	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Cardiac disorders Myocardial Infarction	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Cardiac disorders Pericarditis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Eye disorders Cataract	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Abdominal Pain	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Acute Abdomen	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Anal Fistula	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Colitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Colitis Ulcerative	3.7% 4/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 2/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.1% 15/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.4% 6/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Diarrhoea Haemorrhagic	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Inflammatory Bowel Disease	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Mucosal Prolapse Syndrome	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Pancreatitis Acute	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Pancreatitis Chronic	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Umbilical Hernia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Death	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Pyrexia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Hepatobiliary disorders Cholecystitis Chronic	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Abscess	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Adenovirus Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Anal Abscess	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Appendicitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Bacterial Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Clostridium Difficile Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Complicated Appendicitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Covid-19	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Cytomegalovirus Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Diverticulitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Gastroenteritis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Herpes Zoster	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Pelvic Inflammatory Disease	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Rotavirus Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Staphylococcal Sepsis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Injury, poisoning and procedural complications Craniocerebral Injury	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Injury, poisoning and procedural complications Incarcerated Incisional Hernia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Injury, poisoning and procedural complications Incisional Hernia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Injury, poisoning and procedural complications Postoperative Respiratory Failure	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Guillain-Barre Syndrome	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear Cell Renal Cell Carcinoma	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of Breast	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Haemorrhagic Stroke	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Syncope	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Transient Ischaemic Attack	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Psychiatric disorders Acute Psychosis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Psychiatric disorders Anxiety	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Psychiatric disorders Depression	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Renal and urinary disorders Calculus Urinary	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Renal and urinary disorders Ureterolithiasis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Reproductive system and breast disorders Labia Enlarged	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Reproductive system and breast disorders Vaginal Polyp	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Vascular disorders Hypertension	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Vascular disorders Hypertensive Emergency	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.

Other adverse events

Other adverse events
Measure	IS-1: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=108 participants at risk Participants received single dose of placebo (matching to guselkumab) intravenous (IV) infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=108 participants at risk Participants received single dose of guselkumab 200 milligrams (mg) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 1: Guselkumab 400 mg IV at Weeks I-0, I-4 and I-8 n=111 participants at risk Participants received single dose of guselkumab 400 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study and participants who did not achieve clinical response at Week I-12 entered IS-1 Period 2.	IS-1: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 n=67 participants at risk Participants who initially received placebo and did not achieve clinical response at IS-1 Period 1 Week I-12 were crossed over to guselkumab and received single dose of guselkumab 200 mg IV infusion and placebo (matching to guselkumab) subcutaneous (SC) injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-1: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 n=79 participants at risk Participants who initially received guselkumab 200 mg or 400 mg IV infusion and did not achieve clinical response at IS-1 Period 1 Week I-12 received single dose of guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 1: Placebo IV at Weeks I-0, I-4 and I-8 n=295 participants at risk Participants received single dose of placebo (matched to guselkumab) IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 1: Guselkumab 200 mg IV at Weeks I-0, I-4 and I-8 n=440 participants at risk Participants received single dose of guselkumab 200 mg IV infusion at Weeks I-0, I-4 and I-8. At Week I-12, participants were evaluated for clinical response. Participants who achieved clinical response at Week I-12 entered the maintenance study. Participants who did not achieve clinical response at Week I-12 entered IS-2 Period 2.	IS-2: Period 2: Guselkumab 200 mg IV at Weeks I-12, I-16 and I-20 n=171 participants at risk Participants who initially received placebo and did not achieve clinical response at Week I-12 were crossed over to guselkumab and received guselkumab 200 mg IV infusion and placebo (matching to guselkumab) SC injection at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	IS-2: Period 2: Guselkumab 200 mg SC at Weeks I-12, I-16 and I-20 n=129 participants at risk Participants who initially received guselkumab 200 mg IV infusion and did not achieve clinical response at Week I-12 received guselkumab 200 mg SC injection and placebo (matching to guselkumab) IV infusion at Weeks I-12, I-16 and I-20. At Week I-24, participants were re-evaluated for clinical response. Participants who achieved clinical response at Week I-24 entered the maintenance study. Participants who did not achieve clinical response at Week I-24 received no further study drug and had a safety follow-up up to 12 weeks after their last dose of study drug.	MS: Randomized: Placebo SC Every 4 Weeks (q4w) n=203 participants at risk Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive placebo (matching to guselkumab) SC injection every 4 weeks (q4w) starting from Week M-0 till Week M-40.	MS: Randomized: Guselkumab 100 mg SC q8w n=197 participants at risk Participants who achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) (previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 100 mg SC injection q8w starting from Week M-4 till Week M-36.	MS: Randomized: Guselkumab 200 mg SC q4w n=199 participants at risk Participants who achieved clinical response at IS-1or IS-2 Week I-12 (Period 1)(previously treated with guselkumab) or at Week I-24 (Period 2) (previously treated with placebo and crossover to guselkumab at Week I-12) were randomized to receive guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Placebo SC q4w n=122 participants at risk Participants who were treated previously with placebo (matched to guselkumab) and achieved clinical response at IS-1 or IS-2 Week I-12 (Period 1) entered in MS and received placebo (matched to guselkumab) SC injection q4w starting from Week M-0 till Week M-40.	MS: Nonrandomized: Guselkumab 200 mg SC q4w n=125 participants at risk Participants who were randomized to guselkumab and did not achieve clinical response at IS-1 or IS-2 Week I-12 (period 1) but achieved clinical response at IS-1 or IS-2 Week I-24 (Period 2) entered in MS and received guselkumab 200 mg SC injection q4w starting from Week M-0 till Week M-40.	MS: Dose Adjustment: Placebo SC q4w to Guselkumab 200 mg SC q4w n=75 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive placebo (matched to guselkumab) SC injection and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Dose Adjustment: Guselkumab 100 mg SC q8w to Guselkumab 200 mg SC q4w n=23 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive guselkumab 100 mg SC injection q4w and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w from the time of dose adjustment through maintenance Week 40.	MS: Dose Adjustment: Guselkumab 200 mg SC q4w to Guselkumab 200 mg SC q4w n=31 participants at risk Participants who achieved clinical response in IS-1 or IS-2 (at Week I-12 or Week I-24) and randomized in MS to receive guselkumab 200 mg SC injection q4w and met criteria for loss of clinical response (i.e., no longer satisfied the definition of clinical response) underwent single blinded dose adjustment (between Weeks M-8 and M-32) and received guselkumab 200 mg SC injection q4w (sham dose adjustment) from the time of dose adjustment through maintenance Week 40.
Gastrointestinal disorders Haemorrhoids Thrombosed	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Blood and lymphatic system disorders Anaemia	10.2% 11/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	7.4% 8/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.1% 9/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.0% 4/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 2/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.8% 20/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.0% 22/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.3% 4/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.7% 6/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 5/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 5/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 6/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 5/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.8% 6/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 3/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.7% 2/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Blood and lymphatic system disorders Iron Deficiency Anaemia	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 2/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 2/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Blood and lymphatic system disorders Lymphopenia	4.6% 5/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.8% 2/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.7% 5/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 5/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Ear and labyrinth disorders Motion Sickness	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Ear and labyrinth disorders Tinnitus	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Abdominal Pain	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.7% 4/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 3/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 6/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 4/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 5/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 6/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.4% 3/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Colitis Ulcerative	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 3/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 2/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.8% 3/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 12/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.1% 5/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 7/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.4% 7/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	29.1% 59/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	10.2% 20/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	13.1% 26/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	21.3% 26/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	16.8% 21/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	9.3% 7/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.7% 2/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	16.1% 5/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Colon Dysplasia	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Diarrhoea	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.7% 4/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 3/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Dyspepsia	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 3/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 3/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.4% 3/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Gastrointestinal disorders Haemorrhoids	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.8% 2/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 3/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.7% 2/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Fatigue	4.6% 5/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 3/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 6/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Injection Site Erythema	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 4/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Injection Site Hypersensitivity	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Injection Site Induration	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Injection Site Reaction	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.5% 7/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
General disorders Pyrexia	4.6% 5/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 2/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 3/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.8% 8/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 6/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.6% 7/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.5% 9/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.3% 4/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.4% 8/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Hepatobiliary disorders Hepatic Function Abnormal	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Acute Sinusitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 3/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Candida Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Conjunctivitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Covid-19	4.6% 5/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.6% 6/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.8% 2/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.4% 13/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.0% 22/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	7.6% 13/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	7.0% 9/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	13.8% 28/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	14.2% 28/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	10.1% 20/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	15.6% 19/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	18.4% 23/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.7% 5/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	13.0% 3/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.5% 2/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Herpes Virus Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Influenza	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.8% 6/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Laryngitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Nasopharyngitis	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 8/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.4% 6/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.9% 5/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.3% 3/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.9% 10/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 8/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.5% 7/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	7.4% 9/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.6% 7/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 3/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Sinusitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 4/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 2/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Tinea Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Tonsillitis	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 5/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.7% 2/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.5% 3/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.1% 5/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.2% 2/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.9% 8/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 6/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	7.5% 15/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 5/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 2/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Urinary Tract Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 2/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 7/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 4/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 3/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Infections and infestations Viral Infection	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Investigations White Blood Cell Count Increased	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 3/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Metabolism and nutrition disorders Decreased Appetite	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Metabolism and nutrition disorders Iron Deficiency	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 2/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.4% 3/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Musculoskeletal and connective tissue disorders Arthralgia	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.6% 4/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 6/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 7/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.2% 2/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.4% 13/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.1% 12/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.0% 16/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 5/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 5/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Musculoskeletal and connective tissue disorders Back Pain	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.5% 5/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 8/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 5/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.4% 3/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Musculoskeletal and connective tissue disorders Myalgia	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 2/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.91% 4/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.4% 3/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Dizziness	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 2/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Nervous system disorders Headache	7.4% 8/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.4% 6/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 2/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.8% 3/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.7% 8/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.0% 13/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	5.9% 12/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.1% 8/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.5% 9/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	6.6% 8/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 5/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.0% 3/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	8.7% 2/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Psychiatric disorders Anxiety	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 1/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.45% 2/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Psychiatric disorders Insomnia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.68% 3/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.58% 1/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.0% 2/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.82% 1/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Reproductive system and breast disorders Ejaculation Disorder	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 4/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Skin and subcutaneous tissue disorders Acne	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.93% 1/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.51% 1/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Skin and subcutaneous tissue disorders Night Sweats	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.2% 1/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.23% 1/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.49% 1/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.80% 1/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Skin and subcutaneous tissue disorders Rash	1.9% 2/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.8% 3/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.90% 1/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.4% 4/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 9/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.2% 2/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.78% 1/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.99% 2/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.5% 3/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	2.0% 4/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	3.3% 4/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.6% 2/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	1.3% 1/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Skin and subcutaneous tissue disorders Skin Exfoliation	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.50% 1/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.
Vascular disorders Phlebitis	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/108 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/111 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/67 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/79 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.34% 1/295 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/440 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/171 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/129 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/203 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/197 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/199 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/122 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/125 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/75 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	4.3% 1/23 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.	0.00% 0/31 • IS-1 and 2 Period 1: From Week I-0 to Week I-12; IS-1 and 2 Period 2: From Week I-12 to 12 weeks after last dose of study drug (up to 32 weeks); MS: from Week M-0 up to Week M-44 All-cause mortality:Analyzed on all randomized (IS-1 \& 2) and enrolled participants (MS). SAEs/Other AEs:IS-1 \& 2:All treated analysis set:all randomized participants (regardless of MMS), received at least 1 dose of drug, MS:Safety all randomized and treated analysis set:all participants (regardless of MMS) randomized and received at least 1 dose drug; Safety all nonrandomized and treated analysis set:all non-randomized participants (regardless of MMS) in MS and received at least 1 dose of drug.

Additional Information

Medical Director IMM

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER