Trial Outcomes & Findings for A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (NCT NCT04225715)

Last Updated: 2025-09-19

Results Overview

HBsAg loss was defined as quantitative HBsAg \<0.05 international units/milliliters (IU/mL). The percentage of participants with HBsAg loss was calculated as number of participants with HBsAg loss / total number of participants \*100. 95% confidence interval (CI) was calculated using the Clopper-Pearson method. Percentages have been rounded off.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

281 participants

Primary outcome timeframe

Follow-up Week (FUW) 24

Results posted on

2025-09-19

Participant Flow

A total of 281 participants with chronic hepatitis B (CHB) who had virologic suppression with Nucleos(t)ide (NUC) therapy took part in the study across 13 countries from 05 July 2020 to 19 July 2024.

The study consisted of a screening phase, followed by up to 48 weeks of treatment and up to 48 weeks of post-treatment follow-up. Multiple new combination therapies were compared against a common control. Combos 1, 5, 7 and 8 were prematurely terminated by the Sponsor.

Participant milestones

Participant milestones
Measure	NUC Control Arm Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received core protein allosteric modulator (CpAM), 600 milligrams (mg) tablets, orally, once daily (QD) for 48 weeks and toll-like receptor 7 (TLR7) agonist, 150 mg, orally, once every other day (QOD) during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received short interfering ribonucleic acid (siRNA), 100 mg, as a subcutaneous (SC) injection, every 4 weeks (Q4W) in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and pegylated interferon (PEG-IFN), 180 micrograms (µg), as a SC injection, every week (QW) in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and programmed death ligand-1 locked nucleic acid (PD-L1 LNA), 2 milligrams/kilograms (mg/kg), as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.
Overall Study STARTED	36	38	30	30	30	19	34	33	31
Overall Study COMPLETED	30	37	29	30	27	9	33	15	12
Overall Study NOT COMPLETED	6	1	1	0	3	10	1	18	19

Reasons for withdrawal

Reasons for withdrawal
Measure	NUC Control Arm Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received core protein allosteric modulator (CpAM), 600 milligrams (mg) tablets, orally, once daily (QD) for 48 weeks and toll-like receptor 7 (TLR7) agonist, 150 mg, orally, once every other day (QOD) during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received short interfering ribonucleic acid (siRNA), 100 mg, as a subcutaneous (SC) injection, every 4 weeks (Q4W) in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and pegylated interferon (PEG-IFN), 180 micrograms (µg), as a SC injection, every week (QW) in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and programmed death ligand-1 locked nucleic acid (PD-L1 LNA), 2 milligrams/kilograms (mg/kg), as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.
Overall Study Reason not Specified	1	0	0	0	0	0	0	0
Overall Study Protocol Violation	1	0	0	0	9	0	0	0
Overall Study Withdrawal by Subject	4	1	1	3	1	1	1	0
Overall Study Adverse Event	0	0	0	0	0	0	0	1
Overall Study Arm Terminated By Sponsor	0	0	0	0	0	0	17	18

Baseline Characteristics

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NUC Control Arm n=36 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=38 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=19 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Total n=281 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants	38 Participants n=7 Participants	28 Participants n=5 Participants	29 Participants n=4 Participants	30 Participants n=21 Participants	19 Participants n=10 Participants	34 Participants n=115 Participants	33 Participants n=24 Participants	30 Participants n=42 Participants	277 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	4 Participants n=42 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	4 Participants n=115 Participants	10 Participants n=24 Participants	6 Participants n=42 Participants	58 Participants n=42 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	20 Participants n=4 Participants	25 Participants n=21 Participants	14 Participants n=10 Participants	30 Participants n=115 Participants	23 Participants n=24 Participants	25 Participants n=42 Participants	223 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	37 Participants n=7 Participants	30 Participants n=5 Participants	30 Participants n=4 Participants	30 Participants n=21 Participants	19 Participants n=10 Participants	34 Participants n=115 Participants	33 Participants n=24 Participants	30 Participants n=42 Participants	278 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	33 Participants n=5 Participants	34 Participants n=7 Participants	26 Participants n=5 Participants	29 Participants n=4 Participants	30 Participants n=21 Participants	19 Participants n=10 Participants	32 Participants n=115 Participants	22 Participants n=24 Participants	22 Participants n=42 Participants	247 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	5 Participants n=42 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	9 Participants n=24 Participants	8 Participants n=42 Participants	26 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants

PRIMARY outcome

Timeframe: Follow-up Week (FUW) 24

Population: Modified Intent to Treat (mITT) population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=35 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 24 Weeks Post-End of Treatment (EOT)	0 percentage of participants Interval 0.0 to 10.0	0 percentage of participants Interval 0.0 to 0.0	6.7 percentage of participants Interval 0.8 to 22.1	3.3 percentage of participants Interval 0.1 to 17.2	23.3 percentage of participants Interval 9.9 to 42.3	0 percentage of participants Interval 0.0 to 0.0	11.8 percentage of participants Interval 3.3 to 27.5	0 percentage of participants Interval 0.0 to 10.6	6.7 percentage of participants Interval 0.8 to 22.1

SECONDARY outcome

Timeframe: Combos 1 and 5: Weeks 24, 36, 48 and FUW 48; Combos 2, 3, 4, 6 and NUC Arm: Week 48 and FUW 48; Combo 7: Week 24; Combo 8: Week 36

Population: mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants with data available for analysis. Number analyzed included participants with data available for analysis at that specified timepoint.

HBsAg loss was defined as quantitative HBsAg \<0.05 IU/mL. The percentage of participants with HBsAg loss was calculated as number of participants with HBsAg loss / total number of participants \*100. 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=36 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=4 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Percentage of Participants With HBsAg Loss Week 24	—	0 percentage of participants Interval 0.0 to 0.0	—	—	—	0 percentage of participants Interval 0.0 to 0.0	—	6.1 percentage of participants Interval 0.7 to 20.2	—
Percentage of Participants With HBsAg Loss Week 36	—	0 percentage of participants Interval 0.0 to 0.0	—	—	—	0 percentage of participants Interval 0.0 to 0.0	—	—	13.3 percentage of participants Interval 3.8 to 30.7
Percentage of Participants With HBsAg Loss Week 48	0 percentage of participants Interval 0.0 to 10.0	0 percentage of participants Interval 0.0 to 0.0	6.7 percentage of participants Interval 0.8 to 22.1	3.3 percentage of participants Interval 0.1 to 17.2	30 percentage of participants Interval 14.7 to 49.4	0 percentage of participants Interval 0.0 to 0.0	17.6 percentage of participants Interval 6.8 to 34.5	—	—
Percentage of Participants With HBsAg Loss FUW 48	2.9 percentage of participants Interval 0.1 to 14.9	0 percentage of participants Interval 0.0 to 0.0	10 percentage of participants Interval 2.1 to 26.5	0 percentage of participants Interval 0.0 to 11.6	16.7 percentage of participants Interval 5.6 to 34.7	0 percentage of participants Interval 0.0 to 0.0	11.8 percentage of participants Interval 3.3 to 27.5	—	—

SECONDARY outcome

Timeframe: Combos 1 and 5: Weeks 24, 36, 48, FUW 24 and FUW 48; Combos 2, 3, 4, 6 and NUC Arm: Week 48, FUW 24 and FUW 48; Combo 7: Week 24 and FUW 24; Combo 8: Week 36 and FUW 24

HBsAg seroconversion was defined as a quantitative HBsAg \< 0.05 IU/mL and a positive anti-HBs antibody (defined as per assay reactive threshold anti-HBs ≥10 IU/L). 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=36 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Percentage of Participants With HBsAg Seroconversion Week 24	—	0 percentage of participants Interval 0.0 to 0.0	—	—	—	0 percentage of participants Interval 0.0 to 0.0	—	0 percentage of participants Interval 0.0 to 10.6	—
Percentage of Participants With HBsAg Seroconversion Week 36	—	0 percentage of participants Interval 0.0 to 0.0	—	—	—	0 percentage of participants Interval 0.0 to 0.0	—	—	0 percentage of participants Interval 0.0 to 11.9
Percentage of Participants With HBsAg Seroconversion Week 48	0 percentage of participants Interval 0.0 to 10.0	0 percentage of participants Interval 0.0 to 0.0	3.3 percentage of participants Interval 0.1 to 17.2	0 percentage of participants Interval 0.0 to 11.6	23.3 percentage of participants Interval 9.9 to 42.3	0 percentage of participants Interval 0.0 to 0.0	0 percentage of participants Interval 0.0 to 10.3	—	—
Percentage of Participants With HBsAg Seroconversion FUW 24	0 percentage of participants Interval 0.0 to 10.0	0 percentage of participants Interval 0.0 to 0.0	3.3 percentage of participants Interval 0.1 to 17.2	0 percentage of participants Interval 0.0 to 11.6	20 percentage of participants Interval 7.7 to 38.6	0 percentage of participants Interval 0.0 to 0.0	3.1 percentage of participants Interval 0.1 to 16.2	0 percentage of participants Interval 0.0 to 10.9	0 percentage of participants Interval 0.0 to 11.6
Percentage of Participants With HBsAg Seroconversion FUW 48	2.9 percentage of participants Interval 0.1 to 14.9	0 percentage of participants Interval 0.0 to 0.0	3.3 percentage of participants Interval 0.1 to 17.2	0 percentage of participants Interval 0.0 to 11.6	16.7 percentage of participants Interval 5.6 to 34.7	0 percentage of participants Interval 0.0 to 0.0	5.9 percentage of participants Interval 0.7 to 19.7	—	—

SECONDARY outcome

Timeframe: Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48

Population: mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants from the mITT population who were positive for HBeAg at baseline. Number analyzed included participants with data available for analysis at that specified timepoint.

HBeAg loss was defined as negative /non-reactive HBeAg level. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=8 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=8 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=9 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=8 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=12 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=7 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=10 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=5 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants Week 12	0 percentage of participants	0 percentage of participants	22.2 percentage of participants	50 percentage of participants	33.3 percentage of participants	28.6 percentage of participants	30 percentage of participants	11.1 percentage of participants	40 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants Week 24	0 percentage of participants	0 percentage of participants	37.5 percentage of participants	50 percentage of participants	41.7 percentage of participants	50 percentage of participants	28.6 percentage of participants	11.1 percentage of participants	40 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants Week 36	14.3 percentage of participants	0 percentage of participants	44.4 percentage of participants	25 percentage of participants	55.6 percentage of participants	—	50 percentage of participants	—	40 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants Week 48	12.5 percentage of participants	20 percentage of participants	44.4 percentage of participants	62.5 percentage of participants	54.5 percentage of participants	50 percentage of participants	50 percentage of participants	—	—
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants FUW 12	16.7 percentage of participants	0 percentage of participants	42.9 percentage of participants	62.5 percentage of participants	54.5 percentage of participants	33.3 percentage of participants	44.4 percentage of participants	11.1 percentage of participants	20 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants FUW 24	14.3 percentage of participants	0 percentage of participants	12.5 percentage of participants	50 percentage of participants	36.4 percentage of participants	66.7 percentage of participants	44.4 percentage of participants	11.1 percentage of participants	60 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants FUW 36	12.5 percentage of participants	0 percentage of participants	12.5 percentage of participants	50 percentage of participants	27.3 percentage of participants	—	33.3 percentage of participants	0 percentage of participants	66.7 percentage of participants
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss in Baseline HBeAg-positive Participants FUW 48	14.3 percentage of participants	25 percentage of participants	33.3 percentage of participants	50 percentage of participants	27.3 percentage of participants	—	44.4 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 12, 24, 36, and 48; FUW 12, 24, 36, and 48

Population: mITT population included participants who were randomized and received at least one dose of each drug for their assigned treatment regimen. Overall number analyzed included participants from the mITT population who were positive for HBeAg at baseline. Number analyzed included participants with data available for analysis at that specified timepoint.

HBeAg seroconversion was defined as a negative /non-reactive HBeAg level and a positive anti-HBe antibody. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=8 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=8 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=9 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=8 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=12 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=7 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=10 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=5 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants Week 12	0 percentage of participants	0 percentage of participants	11.1 percentage of participants	0 percentage of participants	8.3 percentage of participants	14.3 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants Week 24	0 percentage of participants	0 percentage of participants	0 percentage of participants	12.5 percentage of participants	8.3 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants Week 36	0 percentage of participants	0 percentage of participants	11.1 percentage of participants	0 percentage of participants	11.1 percentage of participants	—	10 percentage of participants	—	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants Week 48	0 percentage of participants	0 percentage of participants	11.1 percentage of participants	12.5 percentage of participants	18.2 percentage of participants	0 percentage of participants	10 percentage of participants	—	—
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants FUW 12	16.7 percentage of participants	0 percentage of participants	14.3 percentage of participants	12.5 percentage of participants	18.2 percentage of participants	0 percentage of participants	11.1 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants FUW 24	14.3 percentage of participants	0 percentage of participants	0 percentage of participants	25 percentage of participants	9.1 percentage of participants	33.3 percentage of participants	11.1 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants FUW 36	12.5 percentage of participants	0 percentage of participants	0 percentage of participants	25 percentage of participants	9.1 percentage of participants	—	11.1 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With HBeAg Seroconversion in Baseline HBeAg-positive Participants FUW 48	14.3 percentage of participants	0 percentage of participants	11.1 percentage of participants	37.5 percentage of participants	9.1 percentage of participants	—	33.3 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: FUW 12, 24, 36, and 48

Chronic HBV infection is characterized by high levels of circulating HBV DNA. Therefore, HBV levels are indicative of virological response. At screening participants were on NUC therapy and had circulating HBV DNA levels below the assay LLOQ or below 20 IU/mL for at least 6 months. The emergence of a virological breakthrough (HBV DNA \>100 IU/mL or \>1 log increase from nadir) while on NUC therapy, or the emergence of a virological relapse (\>2,000 IU/mL) in participants taken off NME combination and NUC therapy during follow-up, was monitored through the quantification of HBV DNA in plasma.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=35 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: ON NUC (≥ 200 - < 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: ON NUC (≥ 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: OFF NUC (< LLOQ)	0 Participants	—	3 Participants	4 Participants	4 Participants	—	7 Participants	2 Participants	4 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: OFF NUC (≥ LLOQ - < 200 IU/mL)	1 Participants	—	1 Participants	1 Participants	0 Participants	—	2 Participants	1 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: OFF NUC (≥ 200 - < 2000 IU/mL)	0 Participants	—	1 Participants	1 Participants	1 Participants	—	1 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: OFF NUC (≥ 2000 IU/mL)	0 Participants	—	0 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: ON NUC (< LLOQ)	28 Participants	32 Participants	19 Participants	23 Participants	21 Participants	8 Participants	20 Participants	30 Participants	24 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: ON NUC (≥ LLOQ - < 200 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: ON NUC (≥ 200 - < 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 12: ON NUC (≥ 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: OFF NUC (< LLOQ)	0 Participants	—	2 Participants	3 Participants	6 Participants	—	5 Participants	5 Participants	6 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: OFF NUC (≥ LLOQ - < 200 IU/mL)	1 Participants	—	2 Participants	0 Participants	0 Participants	—	5 Participants	2 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: OFF NUC (≥ 200 - < 2000 IU/mL)	0 Participants	—	0 Participants	2 Participants	1 Participants	—	2 Participants	1 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: OFF NUC (≥ 2000 IU/mL)	1 Participants	—	0 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: ON NUC (< LLOQ)	27 Participants	35 Participants	22 Participants	24 Participants	20 Participants	9 Participants	21 Participants	24 Participants	21 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: ON NUC (≥ LLOQ - < 200 IU/mL)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: ON NUC (≥ 200 - < 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 24: ON NUC (≥ 2000 IU/mL)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: OFF NUC (< LLOQ)	0 Participants	—	1 Participants	3 Participants	6 Participants	—	1 Participants	5 Participants	3 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: OFF NUC (≥ LLOQ - < 200 IU/mL)	0 Participants	—	1 Participants	0 Participants	0 Participants	—	3 Participants	0 Participants	2 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: OFF NUC (≥ 200 - < 2000 IU/mL)	1 Participants	—	0 Participants	2 Participants	0 Participants	—	5 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: OFF NUC (≥ 2000 IU/mL)	0 Participants	—	1 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: ON NUC (< LLOQ)	29 Participants	31 Participants	24 Participants	25 Participants	21 Participants	1 Participants	22 Participants	16 Participants	13 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 36: ON NUC (≥ LLOQ - < 200 IU/mL)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: OFF NUC (< LLOQ)	—	—	0 Participants	5 Participants	3 Participants	—	3 Participants	4 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: OFF NUC (≥ LLOQ - < 200 IU/mL)	—	—	1 Participants	0 Participants	3 Participants	—	4 Participants	1 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: OFF NUC (≥ 200 - < 2000 IU/mL)	—	—	1 Participants	2 Participants	0 Participants	—	2 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: OFF NUC (≥ 2000 IU/mL)	—	—	0 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: ON NUC (< LLOQ)	30 Participants	28 Participants	27 Participants	23 Participants	21 Participants	1 Participants	23 Participants	10 Participants	7 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: ON NUC (≥ LLOQ - < 200 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: ON NUC (≥ 200 - < 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantification (LLOQ), <200 IU/mL, and <2,000 IU/mL FUW 48: ON NUC (≥ 2000 IU/mL)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: HBsAg, Anti-HBs, HBeAg & HBV RNA: Combo 1 to 6 and NUC arm: Weeks 24, 36, 48, FUW 24 and FUW 48; Combo 7: Week 24, FUW 24 & FUW 48; Combo 8: Weeks 24, 36, FUW 24 & FUW 48; HBV DNA: FUW 24 and FUW 48

The serological markers of HBV infection include viral antigens (HBsAg \& HBeAg) and antibody (anti-HBs). Changes in serological markers and efficacy biomarkers (HBV RNA) from baseline are reported. Change from baseline for HBV DNA was assessed in 'ON NUC' participants.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=36 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=9 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBsAg: Week 24	-0.08 log10 IU/mL Standard Deviation 0.16	-0.11 log10 IU/mL Standard Deviation 0.26	-1.49 log10 IU/mL Standard Deviation 0.56	-1.78 log10 IU/mL Standard Deviation 0.59	-1.89 log10 IU/mL Standard Deviation 1.05	-1.38 log10 IU/mL Standard Deviation 0.41	-1.74 log10 IU/mL Standard Deviation 0.62	-2.12 log10 IU/mL Standard Deviation 0.73	-1.8 log10 IU/mL Standard Deviation 0.49
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBsAg: Week 36	-0.08 log10 IU/mL Standard Deviation 0.13	-0.13 log10 IU/mL Standard Deviation 0.23	-1.52 log10 IU/mL Standard Deviation 0.67	-1.93 log10 IU/mL Standard Deviation 0.47	-2.14 log10 IU/mL Standard Deviation 1.27	-1.51 log10 IU/mL Standard Deviation NA Since only 1 participant was analyzed, standard deviation (SD) could not be calculated.	-1.71 log10 IU/mL Standard Deviation 0.69	—	-2.08 log10 IU/mL Standard Deviation 0.63
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBsAg: Week 48	-0.2 log10 IU/mL Standard Deviation 0.52	-0.09 log10 IU/mL Standard Deviation 0.12	-1.58 log10 IU/mL Standard Deviation 0.63	-1.93 log10 IU/mL Standard Deviation 0.6	-2.22 log10 IU/mL Standard Deviation 1.16	-1.3 log10 IU/mL Standard Deviation 0.45	-2.18 log10 IU/mL Standard Deviation 0.86	—	—
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBsAg: FUW 24	-0.19 log10 IU/mL Standard Deviation 0.35	-0.18 log10 IU/mL Standard Deviation 0.31	-1.19 log10 IU/mL Standard Deviation 0.76	-1.71 log10 IU/mL Standard Deviation 0.75	-1.71 log10 IU/mL Standard Deviation 1.24	-1.5 log10 IU/mL Standard Deviation 0.89	-1.47 log10 IU/mL Standard Deviation 0.81	-1.3 log10 IU/mL Standard Deviation 0.7	-1.46 log10 IU/mL Standard Deviation 0.74
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBsAg: FUW 48	-0.25 log10 IU/mL Standard Deviation 0.43	-0.25 log10 IU/mL Standard Deviation 0.36	-0.89 log10 IU/mL Standard Deviation 0.76	-1.2 log10 IU/mL Standard Deviation 0.84	-1.28 log10 IU/mL Standard Deviation 1.12	-2.02 log10 IU/mL Standard Deviation NA Since only 1 participant was analyzed, SD could not be calculated.	-1.01 log10 IU/mL Standard Deviation 0.8	-0.91 log10 IU/mL Standard Deviation 0.69	-1.14 log10 IU/mL Standard Deviation 0.83
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time Anti-HBs: Week 24	-0.01 log10 IU/mL Standard Deviation 0.04	-0.01 log10 IU/mL Standard Deviation 0.08	0.06 log10 IU/mL Standard Deviation 0.32	0 log10 IU/mL Standard Deviation 0	0.03 log10 IU/mL Standard Deviation 0.2	0.06 log10 IU/mL Standard Deviation 0.13	-0.01 log10 IU/mL Standard Deviation 0.04	0.01 log10 IU/mL Standard Deviation 0.12	-0.03 log10 IU/mL Standard Deviation 0.1
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time Anti-HBs: Week 36	-0.01 log10 IU/mL Standard Deviation 0.02	-0.02 log10 IU/mL Standard Deviation 0.09	0.06 log10 IU/mL Standard Deviation 0.34	0 log10 IU/mL Standard Deviation 0	0.3 log10 IU/mL Standard Deviation 0.69	0 log10 IU/mL Standard Deviation NA Since only 1 participant was analyzed, SD could not be calculated.	-0.07 log10 IU/mL Standard Deviation 0.27	—	-0.03 log10 IU/mL Standard Deviation 0.11
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time Anti-HBs: Week 48	0 log10 IU/mL Standard Deviation 0.01	-0.04 log10 IU/mL Standard Deviation 0.11	0.06 log10 IU/mL Standard Deviation 0.35	0 log10 IU/mL Standard Deviation 0	0.55 log10 IU/mL Standard Deviation 0.96	0.01 log10 IU/mL Standard Deviation 0.02	-0.05 log10 IU/mL Standard Deviation 0.27	—	—
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time Anti-HBs: FUW 24	-0.02 log10 IU/mL Standard Deviation 0.08	-0.01 log10 IU/mL Standard Deviation 0.06	0.05 log10 IU/mL Standard Deviation 0.31	0.01 log10 IU/mL Standard Deviation 0.05	0.63 log10 IU/mL Standard Deviation 1.04	0.09 log10 IU/mL Standard Deviation 0.2	-0.02 log10 IU/mL Standard Deviation 0.41	0.01 log10 IU/mL Standard Deviation 0.1	-0.06 log10 IU/mL Standard Deviation 0.2
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time Anti-HBs: FUW 48	0.04 log10 IU/mL Standard Deviation 0.33	-0.01 log10 IU/mL Standard Deviation 0.04	0.01 log10 IU/mL Standard Deviation 0.28	0.02 log10 IU/mL Standard Deviation 0.12	0.41 log10 IU/mL Standard Deviation 0.93	0 log10 IU/mL Standard Deviation NA Since only 1 participant was analyzed, SD could not be calculated.	0.04 log10 IU/mL Standard Deviation 0.49	0.09 log10 IU/mL Standard Deviation 0.26	0.02 log10 IU/mL Standard Deviation 0.07
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBeAg: Week 24	-0.08 log10 IU/mL Standard Deviation 0.1	-0.04 log10 IU/mL Standard Deviation 0.13	-0.39 log10 IU/mL Standard Deviation 0.16	-0.4 log10 IU/mL Standard Deviation 0.21	-0.37 log10 IU/mL Standard Deviation 0.19	-0.19 log10 IU/mL Standard Deviation 0.32	-0.53 log10 IU/mL Standard Deviation 0.3	-0.47 log10 IU/mL Standard Deviation 0.32	-0.46 log10 IU/mL Standard Deviation 0.15
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBeAg: Week 36	-0.08 log10 IU/mL Standard Deviation 0.14	-0.05 log10 IU/mL Standard Deviation 0.04	-0.45 log10 IU/mL Standard Deviation 0.2	-0.53 log10 IU/mL Standard Deviation 0.15	-0.43 log10 IU/mL Standard Deviation 0.2	—	-0.65 log10 IU/mL Standard Deviation 0.44	—	-0.46 log10 IU/mL Standard Deviation 0.26
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBeAg: Week 48	-0.06 log10 IU/mL Standard Deviation 0.15	-0.06 log10 IU/mL Standard Deviation 0.06	-0.48 log10 IU/mL Standard Deviation 0.18	-0.48 log10 IU/mL Standard Deviation 0.2	-0.44 log10 IU/mL Standard Deviation 0.19	-0.28 log10 IU/mL Standard Deviation 0.42	-0.69 log10 IU/mL Standard Deviation 0.44	—	—
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBeAg: FUW 24	-0.19 log10 IU/mL Standard Deviation 0.15	-0.09 log10 IU/mL Standard Deviation 0.12	-0.02 log10 IU/mL Standard Deviation 1.37	-0.42 log10 IU/mL Standard Deviation 0.22	-0.33 log10 IU/mL Standard Deviation 0.19	-0.68 log10 IU/mL Standard Deviation 0.73	-0.56 log10 IU/mL Standard Deviation 0.33	-0.4 log10 IU/mL Standard Deviation 0.37	-0.51 log10 IU/mL Standard Deviation 0.31
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBeAg: FUW 48	-0.36 log10 IU/mL Standard Deviation 0.31	-0.22 log10 IU/mL Standard Deviation 0.11	-0.14 log10 IU/mL Standard Deviation 1.06	-0.38 log10 IU/mL Standard Deviation 0.19	-0.3 log10 IU/mL Standard Deviation 0.16	—	-0.5 log10 IU/mL Standard Deviation 0.38	-0.42 log10 IU/mL Standard Deviation 0.47	—
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV RNA: Week 24	0.09 log10 IU/mL Standard Deviation 0.43	-1.19 log10 IU/mL Standard Deviation 1.19	-0.7 log10 IU/mL Standard Deviation 0.34	-0.95 log10 IU/mL Standard Deviation 0.6	-1.43 log10 IU/mL Standard Deviation 0.89	-1.34 log10 IU/mL Standard Deviation 0.65	-0.92 log10 IU/mL Standard Deviation 0.92	-1.17 log10 IU/mL Standard Deviation 1.26	-0.81 log10 IU/mL Standard Deviation 0.55
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV RNA: Week 36	0.05 log10 IU/mL Standard Deviation 0.3	-1.66 log10 IU/mL Standard Deviation 1.4	-0.74 log10 IU/mL Standard Deviation 0.41	-0.73 log10 IU/mL Standard Deviation 0.57	-1.67 log10 IU/mL Standard Deviation 0.9	—	-0.76 log10 IU/mL Standard Deviation 0.76	—	-0.76 log10 IU/mL Standard Deviation 0.56
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV RNA: Week 48	-0.04 log10 IU/mL Standard Deviation 0.32	-1.66 log10 IU/mL Standard Deviation 1.4	-0.8 log10 IU/mL Standard Deviation 0.48	-0.94 log10 IU/mL Standard Deviation 0.6	-1.43 log10 IU/mL Standard Deviation 0.95	-1.32 log10 IU/mL Standard Deviation 0.68	-0.9 log10 IU/mL Standard Deviation 0.81	—	—
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV RNA: FUW 24	-0.25 log10 IU/mL Standard Deviation 0.28	-0.13 log10 IU/mL Standard Deviation 0.12	-0.68 log10 IU/mL Standard Deviation 0.49	-0.87 log10 IU/mL Standard Deviation 0.59	-0.64 log10 IU/mL Standard Deviation 0.82	-1.04 log10 IU/mL Standard Deviation 0.63	-0.51 log10 IU/mL Standard Deviation 0.63	-0.82 log10 IU/mL Standard Deviation 0.75	-0.81 log10 IU/mL Standard Deviation 0.55
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV RNA: FUW 48	-0.43 log10 IU/mL Standard Deviation 0.6	-0.11 log10 IU/mL Standard Deviation 0.19	-0.6 log10 IU/mL Standard Deviation 0.48	-0.78 log10 IU/mL Standard Deviation 0.55	-0.85 log10 IU/mL Standard Deviation 0.75	—	-0.37 log10 IU/mL Standard Deviation 0.52	-0.98 log10 IU/mL Standard Deviation 0.8	-0.49 log10 IU/mL Standard Deviation 0.57
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV DNA: FUW 24	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of samples being below LLOQ.
Change From Baseline in HBsAg, Anti-HBs, HBeAg, HBV Ribonucleic Acid (RNA) and HBV DNA Levels Over Time HBV DNA: FUW 48	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of the samples being below LLOQ.	NA log10 IU/mL Standard Deviation NA Mean and SD were not estimable due to all of samples being below LLOQ.

SECONDARY outcome

Timeframe: Predose on Day 1 and up to 168 hours post dose (Week 1)

Population: PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample.

The AUC was predicted and summarized by modelling \& simulation via the population pharmacokinetics (PopPK) method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=63 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 7 and 8: Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Week 1 (AUC1-0-168h) of PD-L1 LNA	1047 hoursnanomoles/liters (hrnmol/L) Standard Deviation 273	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 and up to 168 hours post dose (Week 1)

Population: PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample.

The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=63 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 7 and 8: Maximum Plasma Concentration (Cmax) at Week 1 (Cmax1-0-168h) of PD-L1 LNA	163 nanomoles/liters (nmol/L) Standard Deviation 60.8	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)

Population: PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample.

The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. As per planned analysis data was collected and reported in a pooled manner for Combos 7 and 8.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=63 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 7 and 8: AUC Over the Dosing Interval at Week 12 (AUC12-0-168h) of PD-L1 LNA	1143 hr*nmol/L Standard Deviation 286	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Week 12 up to 168 hours post dose (Week 12)

Population: PK population included participants who received at least one dose of the PD-L1 LNA and had at least one evaluable post-baseline PK sample.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=63 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 7 and 8: Cmax at Week 12 (Cmax12-0-168h) of PD-L1 LNA	165 nmol/L Standard Deviation 60.9	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28

Population: PK population included participants who received at least one dose of the siRNA and had at least one evaluable post-baseline PK sample.

The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=30 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=30 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve (AUC) Over Days 1-28 of siRNA	4670 hoursnanograms/millilitres (hrng/mL) Standard Deviation 1112	11098 hoursnanograms/millilitres (hrng/mL) Standard Deviation 2499	11073 hoursnanograms/millilitres (hrng/mL) Standard Deviation 2272	9831 hoursnanograms/millilitres (hrng/mL) Standard Deviation 2215	9780 hoursnanograms/millilitres (hrng/mL) Standard Deviation 1942	9110 hoursnanograms/millilitres (hrng/mL) Standard Deviation 1418	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 and 1-3 and 4-6 hours post dose each day, up to Day 28

Population: PK population included participants who received at least one dose of the siRNA and had at least one evaluable post-baseline PK sample.

The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=30 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=30 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 1-28 of siRNA	190 nanograms/millilitres (ng/mL) Standard Deviation 116	463 nanograms/millilitres (ng/mL) Standard Deviation 203	450 nanograms/millilitres (ng/mL) Standard Deviation 168	408 nanograms/millilitres (ng/mL) Standard Deviation 168	373 nanograms/millilitres (ng/mL) Standard Deviation 149	311 nanograms/millilitres (ng/mL) Standard Deviation 97	—	—	—

SECONDARY outcome

Timeframe: From Day 29 up to Day 56

Population: PK population included participants who received at least one dose of the siRNA and had at least one evaluable post-baseline PK sample.

The AUC tau was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. Simulations for the dosing interval between Day 29 and Day 56 was done using population PK modeling informed by sparse PK samples collected on Days 1, 85, 169, 253, and 337 at predose, 1-3 hours, and 4-6 hours post dose.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=30 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=30 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 2, 3, 4, 6, 7 and 8: Area Under the Plasma Concentration Time Curve During the Dosing Interval (AUC Tau) Over Days 29-56 of siRNA	5401 hr*ng/mL Standard Deviation 1245	12591 hr*ng/mL Standard Deviation 2659	12623 hr*ng/mL Standard Deviation 2428	11207 hr*ng/mL Standard Deviation 2371	11216 hr*ng/mL Standard Deviation 2068	10513 hr*ng/mL Standard Deviation 1511	—	—	—

SECONDARY outcome

Timeframe: From Day 29 up to Day 56

Population: PK population included participants who received at least one dose of the siRNA and had at least one evaluable post-baseline PK sample.

The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples. Simulations for the dosing interval between Day 29 and Day 56 was done using population PK modeling informed by sparse PK samples collected on Days 1, 85, 169, 253, and 337 at predose, 1-3 hours, and 4-6 hours post dose.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=30 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=30 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 2, 3, 4, 6, 7 and 8: Cmax Over Days 29-56 of siRNA	192 ng/mL Standard Deviation 116	468 ng/mL Standard Deviation 204	454 ng/mL Standard Deviation 169	411 ng/mL Standard Deviation 169	376 ng/mL Standard Deviation 150	315 ng/mL Standard Deviation 98	—	—	—

SECONDARY outcome

Timeframe: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36

Population: PK population included participants who received at least one dose of the TLR7 and had at least one evaluable post-baseline PK sample.

The AUC was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=38 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=34 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 1 and 6: AUC of TLR7	3139 ng*hr/mL Standard Deviation 938.8	2813 ng*hr/mL Standard Deviation 75.33	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 1-3 and 4-6 hours post-dose on Days 1, 3, 5 on Weeks 12 and 36

Population: PK population included participants who received at least one dose of the TLR7 and had at least one evaluable post-baseline PK sample.

The Cmax was predicted and summarized by modelling \& simulation via the PopPK method based on pre and post dose samples.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=38 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=34 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 1 and 6: Cmax of TLR7	1548 ng/mL Standard Deviation 419.7	1491 ng/mL Standard Deviation 334.8	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From Day 1 up to end of 48 weeks of follow up (up to approximately 1.8 years)

Population: Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Outcome measures

Outcome measures
Measure	NUC Control Arm n=35 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=38 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=19 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Number of Participants With Adverse Events (AEs)	27 Participants	34 Participants	30 Participants	29 Participants	30 Participants	18 Participants	33 Participants	26 Participants	27 Participants

SECONDARY outcome

Timeframe: From Day 1 up to end of follow up (up to approximately 4 years)

Population: Immunogenicity population included participants who had at least one pre-dose (baseline) or at least one post-dose assessment will be included and analyzed according to the treatment they actually received or were allocated to receive.

Treatment-emergent anti drug antibody (ADA) was defined as participants who seroconverted or experienced a boost in preexisting ADA during the study. Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples were greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).

Outcome measures

Outcome measures
Measure	NUC Control Arm n=30 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=30 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 Participants Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=19 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=34 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=33 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=31 Participants Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 2, 3, 4, 5, 6, 7 and 8: Number of Participants With Anti-siRNA Antibodies	3 Participants	2 Participants	12 Participants	1 Participants	3 Participants	10 Participants	14 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 for Combo 7 and 8 up to end of follow up (Up to approximately 2 years)

Treatment-emergent ADA was defined as participants who seroconverted or experienced a boost in preexisting ADA during the study. Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples were greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).

Outcome measures

Outcome measures
Measure	NUC Control Arm n=33 Participants Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 1: CpAM + TLR7 Agonist + NUC n=31 Participants Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Combos 7 and 8: Number of Participants With Anti-PD-L1 Antibodies	16 Participants	15 Participants	—	—	—	—	—	—	—

Adverse Events

Combo 1: CpAM + TLR7 Agonist + NUC

Serious events: 3 serious events

Other events: 33 other events

Deaths: 0 deaths

Combo 2: siRNA (100 mg) + NUC

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Combo 3: siRNA (200 mg) + NUC

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Combo 4: siRNA + PEG-IFN + NUC

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Combo 5: siRNA + CpAM + NUC

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Combo 6: siRNA + TLR7 Agonist + NUC

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

Combo 7: siRNA + PD-L1 LNA + NUC

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Combo 8: siRNA + PD-L1 LNA + NUC

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

NUC Control Arm

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Combo 1: CpAM + TLR7 Agonist + NUC n=38 participants at risk Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 participants at risk Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=19 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=31 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	NUC Control Arm n=35 participants at risk Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
Eye disorders Diplopia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Large intestine polyp	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Influenza like illness	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Appendicitis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Fascioliasis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Vertebral osteophyte	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign hepatic neoplasm	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neuroendocrine tumour	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Psychiatric disorders Panic reaction	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.

Other adverse events

Other adverse events
Measure	Combo 1: CpAM + TLR7 Agonist + NUC n=38 participants at risk Participants received CpAM, 600 mg tablets, orally, QD for 48 weeks and TLR7 agonist, 150 mg, orally, QOD during Weeks 1-12 and Weeks 25-36 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 2: siRNA (100 mg) + NUC n=30 participants at risk Participants received siRNA, 100 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 3: siRNA (200 mg) + NUC n=30 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 4: siRNA + PEG-IFN + NUC n=30 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W and PEG-IFN, 180 µg, as a SC injection, QW in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 5: siRNA + CpAM + NUC n=19 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W and CpAM, 600 mg tablets, orally, QD in addition to their background NUC therapy for 48 weeks. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 6: siRNA + TLR7 Agonist + NUC n=34 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W for 48 weeks and TLR7 agonist, 150 mg tablets, orally, QOD during Weeks 13-24 and Weeks 37-48 in addition to their background NUC therapy. After Week 48, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 7: siRNA + PD-L1 LNA + NUC n=33 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 13-24 in addition to their background NUC therapy for 24 weeks. After Week 24, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	Combo 8: siRNA + PD-L1 LNA + NUC n=31 participants at risk Participants received siRNA, 200 mg, as a SC injection, Q4W up to Week 24 and PD-L1 LNA, 2 mg/kg, as a SC injection, QW during Weeks 25-36 in addition to their background NUC therapy for 36 weeks. After Week 36, participants continued NUC treatment during follow-up unless the NUC discontinuation criteria were met.	NUC Control Arm n=35 participants at risk Participants continued their background NUC therapy for 48 weeks. Thereafter, in line with current CHB treatment guidelines, participants continued NUC treatment during the follow-up unless the NUC discontinuation criteria were met.
General disorders Vessel puncture site bruise	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Blood and lymphatic system disorders Anaemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Blood and lymphatic system disorders Monocytopenia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Blood and lymphatic system disorders Neutropenia	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	13.3% 4/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Cardiac disorders Atrioventricular block first degree	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Cardiac disorders Sinus arrhythmia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Cardiac disorders Sinus bradycardia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Cardiac disorders Ventricular extrasystoles	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Ear and labyrinth disorders Ear discomfort	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Ear and labyrinth disorders Tinnitus	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Eye disorders Dry eye	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Abdominal discomfort	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Abdominal distension	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	13.3% 4/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Abdominal pain	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.7% 3/31 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Abdominal pain upper	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	21.1% 4/19 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.8% 4/34 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Chronic gastritis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Dental caries	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Diarrhoea	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Flatulence	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Gingival bleeding	5.3% 2/38 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Mouth ulceration	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Nausea	2.6% 1/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Gastrointestinal disorders Periodontal disease	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Asthenia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Chest discomfort	2.6% 1/38 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Chest pain	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Fatigue	13.2% 5/38 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	23.3% 7/30 • Number of events 12 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.1% 3/33 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.7% 3/31 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Influenza like illness	36.8% 14/38 • Number of events 62 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	26.7% 8/30 • Number of events 12 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	47.1% 16/34 • Number of events 38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.9% 4/31 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Injection site reaction	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	30.0% 9/30 • Number of events 16 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	50.0% 15/30 • Number of events 39 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.8% 3/19 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.6% 7/34 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.2% 5/33 • Number of events 9 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	22.6% 7/31 • Number of events 37 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Pain	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Pyrexia	15.8% 6/38 • Number of events 9 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	23.3% 7/30 • Number of events 7 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	21.1% 4/19 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.6% 7/34 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Sensation of foreign body	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
General disorders Thirst	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Bile duct stone	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Cholelithiasis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Hepatic cyst	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Hepatic mass	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Hepatic steatosis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	23.3% 7/30 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.1% 3/33 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.4% 4/35 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Hepatobiliary disorders Liver disorder	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations COVID-19	15.8% 6/38 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	33.3% 10/30 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	53.3% 16/30 • Number of events 17 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	56.7% 17/30 • Number of events 17 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.8% 3/19 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	50.0% 17/34 • Number of events 18 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.1% 3/33 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.9% 4/31 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	22.9% 8/35 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Conjunctivitis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	13.3% 4/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Gastroenteritis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Gingivitis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Hepatitis B reactivation	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	29.4% 10/34 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.1% 4/33 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	22.6% 7/31 • Number of events 7 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.6% 3/35 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Herpes virus infection	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Nasopharyngitis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.9% 4/31 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Pharyngitis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Sinusitis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Infections and infestations Upper respiratory tract infection	10.5% 4/38 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	46.7% 14/30 • Number of events 24 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	36.7% 11/30 • Number of events 16 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	43.3% 13/30 • Number of events 16 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	26.3% 5/19 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.8% 4/34 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.4% 4/35 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Accidental overdose	21.1% 8/38 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.8% 4/34 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Overdose	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.8% 3/19 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.1% 4/33 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Product dose omission issue	5.3% 2/38 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	43.3% 13/30 • Number of events 14 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	46.7% 14/30 • Number of events 14 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	63.3% 19/30 • Number of events 23 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 7 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	44.1% 15/34 • Number of events 33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	37.1% 13/35 • Number of events 13 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Alanine aminotransferase increased	10.5% 4/38 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	43.3% 13/30 • Number of events 22 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	43.3% 13/30 • Number of events 21 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	83.3% 25/30 • Number of events 39 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	52.6% 10/19 • Number of events 16 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	44.1% 15/34 • Number of events 25 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	18.2% 6/33 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	19.4% 6/31 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.6% 3/35 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Amylase increased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 14 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	14.7% 5/34 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.1% 3/33 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Aspartate aminotransferase increased	7.9% 3/38 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 11 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	33.3% 10/30 • Number of events 17 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	70.0% 21/30 • Number of events 32 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	36.8% 7/19 • Number of events 7 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	32.4% 11/34 • Number of events 21 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.1% 4/33 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Blood bilirubin increased	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Blood creatine phosphokinase increased	2.6% 1/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 7 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Blood phosphorus decreased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Blood triglycerides increased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 8 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Blood uric acid increased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.7% 2/35 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Cystatin C increased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Electrocardiogram PR shortened	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Gamma-glutamyltransferase increased	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	23.3% 7/30 • Number of events 9 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Glutamate dehydrogenase increased	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 12 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Lipase increased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.8% 3/19 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.1% 4/33 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Lymphocyte count decreased	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Neutrophil count decreased	10.5% 4/38 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	40.0% 12/30 • Number of events 24 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	17.6% 6/34 • Number of events 11 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Platelet count decreased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	56.7% 17/30 • Number of events 26 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Protein urine present	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	26.7% 8/30 • Number of events 12 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Thyroxine free decreased	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations Weight decreased	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.7% 2/35 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Investigations White blood cell count decreased	10.5% 4/38 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	26.7% 8/30 • Number of events 14 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	14.7% 5/34 • Number of events 11 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Decreased appetite	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 10 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	23.3% 7/30 • Number of events 15 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	11.8% 4/34 • Number of events 11 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Hyperuricaemia	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 9 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	20.0% 6/30 • Number of events 9 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Back pain	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.7% 3/31 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.5% 2/19 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Myalgia	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Nervous system disorders Dizziness	2.6% 1/38 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	14.7% 5/34 • Number of events 12 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Nervous system disorders Headache	13.2% 5/38 • Number of events 24 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.7% 3/31 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Nervous system disorders Hypoaesthesia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Psychiatric disorders Depression	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.3% 1/19 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Psychiatric disorders Insomnia	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Reproductive system and breast disorders Prostatic calcification	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	5.9% 2/34 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	8.8% 3/34 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	12.9% 4/31 • Number of events 4 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 6 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	13.3% 4/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	15.8% 3/19 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/34 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.1% 2/33 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	9.1% 3/33 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	2.9% 1/35 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Skin and subcutaneous tissue disorders Alopecia	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	16.7% 5/30 • Number of events 5 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.7% 2/30 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/38 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	10.0% 3/30 • Number of events 3 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.2% 1/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Skin and subcutaneous tissue disorders Rash	5.3% 2/38 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.3% 1/30 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/33 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/31 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.
Vascular disorders Hypertension	0.00% 0/38 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/30 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/19 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/34 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	3.0% 1/33 • Number of events 1 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	6.5% 2/31 • Number of events 2 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.	0.00% 0/35 • From Day 1 up to end of 48 week follow up (up to approximately 1.8 years) Safety population included participants randomized to a treatment regimen who received at least one dose of any drug for their assigned treatment regimen, whether prematurely withdrawn from the study or not.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER