Trial Outcomes & Findings for Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (NCT NCT03656562)

NCT ID: NCT03656562

Last Updated: 2025-10-07

Results Overview

The primary endpoint is a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders. SRI-4 response is defined as below: * having \>= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND * no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND * \<10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline Sustained reduction in oral corticosteroid is defined as below: * =\< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND * no increase of that dose from Week 17 through Week 29

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 107 participants
• Primary outcome timeframe: Baseline, Week 17 to Week 29
• Results posted on: 2025-10-07

Participant Flow

This study is conducted in 31 centers in 15 countries: Argentina (1), Australia (1), China (3), Czech Republic (1), France (1), Germany (2), Hungary (2), Israel (1), Japan (5), Korea, Republic of (1), Poland (3), Russia (3), Spain (2), Taiwan (3), Thailand (2).

Participant milestones

Measure	Cohort 1 VAY736 Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.
Overall Study STARTED	34	33	20	20
Overall Study Pharmacodynamic Analysis Set	34	33	20	20
Overall Study COMPLETED	11	13	15	14
Overall Study NOT COMPLETED	23	20	5	6

Reasons for withdrawal

Measure	Cohort 1 VAY736 Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.
Overall Study Ongoing at the time of Interim Analysis Cut-off date	19	13	5	4
Overall Study Physician Decision	1	2	0	0
Overall Study Subject Decision	3	5	0	2

Baseline Characteristics

Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients

Baseline characteristics by cohort

Measure	Cohort 1 VAY736 n=34 Participants Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo n=33 Participants Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 n=20 Participants Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo n=20 Participants Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Total n=107 Participants Total of all reporting groups
Age, Continuous	42.0 Years STANDARD_DEVIATION 10.91 • n=5 Participants	39.2 Years STANDARD_DEVIATION 10.46 • n=7 Participants	37.4 Years STANDARD_DEVIATION 11.34 • n=5 Participants	44.7 Years STANDARD_DEVIATION 12.47 • n=4 Participants	40.8 Years STANDARD_DEVIATION 11.29 • n=21 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	27 Participants n=7 Participants	20 Participants n=5 Participants	19 Participants n=4 Participants	98 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants	12 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants	40 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White	25 Participants n=5 Participants	21 Participants n=7 Participants	12 Participants n=5 Participants	8 Participants n=4 Participants	66 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 17 to Week 29

Population: Pharmacodynamic analysis set (PD analysis set)

The primary endpoint is a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders.

SRI-4 response is defined as below:

• having >= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND
• no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND
• <10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline

Sustained reduction in oral corticosteroid is defined as below:

• =< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND
• no increase of that dose from Week 17 through Week 29

Outcome measures

Measure	Cohort 1 VAY736 n=34 Participants Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo n=33 Participants Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 n=20 Participants Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo n=20 Participants Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.
Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29	15 Participants	3 Participants	8 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29

Population: Pharmacodynamic analysis set (PD analysis set). Only participants with a value at both Baseline and post-baseline visit included.

The Physician's global assessment (PhGA-VAS) of disease activity was performed using 100 mm VAS ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.

Outcome measures

Measure	Cohort 1 VAY736 n=34 Participants Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo n=33 Participants Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 n=20 Participants Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo n=20 Participants Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 5	-7.6 Unit on a scale Standard Deviation 14.27	-5.6 Unit on a scale Standard Deviation 13.76	-8.3 Unit on a scale Standard Deviation 12.04	-12.5 Unit on a scale Standard Deviation 15.94
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 9	-17.4 Unit on a scale Standard Deviation 18.72	-10.9 Unit on a scale Standard Deviation 13.54	-9.3 Unit on a scale Standard Deviation 15.73	-13.7 Unit on a scale Standard Deviation 18.43
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 13	-23.0 Unit on a scale Standard Deviation 19.51	-13.6 Unit on a scale Standard Deviation 16.72	-19.4 Unit on a scale Standard Deviation 16.70	-20.3 Unit on a scale Standard Deviation 19.26
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 17	-26.2 Unit on a scale Standard Deviation 19.14	-14.2 Unit on a scale Standard Deviation 16.38	-21.9 Unit on a scale Standard Deviation 21.81	-22.2 Unit on a scale Standard Deviation 20.10
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 21	-28.1 Unit on a scale Standard Deviation 20.27	-17.9 Unit on a scale Standard Deviation 16.24	-26.1 Unit on a scale Standard Deviation 23.15	-24.1 Unit on a scale Standard Deviation 17.71
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 25	-33.2 Unit on a scale Standard Deviation 19.63	-18.6 Unit on a scale Standard Deviation 17.62	-28.5 Unit on a scale Standard Deviation 22.92	-24.6 Unit on a scale Standard Deviation 19.12
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity Week 29	-32.8 Unit on a scale Standard Deviation 20.74	-19.4 Unit on a scale Standard Deviation 16.04	-28.7 Unit on a scale Standard Deviation 22.89	-24.5 Unit on a scale Standard Deviation 19.25

SECONDARY outcome

Timeframe: Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29

Population: Pharmacodynamic analysis set (PD analysis set). Only participants with a value at both Baseline and post-baseline visit included.

The patient's global assessment of disease activity was performed using a Visual Analogue Scale (VAS) of 100 mm ranging from "no disease activity" (score 0) to "severe disease activity" (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.

Outcome measures

Measure	Cohort 1 VAY736 n=34 Participants Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 1 VAY736 Placebo n=33 Participants Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Cohort 2 CFZ533 n=20 Participants Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.	Cohort 2 CFZ533 Placebo n=20 Participants Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49.
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 29	-18.1 Unit on a scale Standard Deviation 21.81	-9.0 Unit on a scale Standard Deviation 24.64	-27.8 Unit on a scale Standard Deviation 33.41	-1.9 Unit on a scale Standard Deviation 25.06
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 5	-9.0 Unit on a scale Standard Deviation 23.14	-4.8 Unit on a scale Standard Deviation 13.60	-9.8 Unit on a scale Standard Deviation 20.63	-3.8 Unit on a scale Standard Deviation 19.33
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 9	-12.5 Unit on a scale Standard Deviation 21.35	-12.2 Unit on a scale Standard Deviation 15.62	-17.9 Unit on a scale Standard Deviation 30.22	0.1 Unit on a scale Standard Deviation 20.52
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 13	-15.7 Unit on a scale Standard Deviation 21.69	-8.8 Unit on a scale Standard Deviation 17.75	-21.8 Unit on a scale Standard Deviation 31.01	-0.1 Unit on a scale Standard Deviation 22.10
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 17	-12.7 Unit on a scale Standard Deviation 24.19	-8.0 Unit on a scale Standard Deviation 19.27	-26.7 Unit on a scale Standard Deviation 28.92	1.6 Unit on a scale Standard Deviation 19.05
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 21	-15.1 Unit on a scale Standard Deviation 24.82	-9.5 Unit on a scale Standard Deviation 24.88	-27.2 Unit on a scale Standard Deviation 31.92	-0.5 Unit on a scale Standard Deviation 24.79
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity Week 25	-18.0 Unit on a scale Standard Deviation 19.91	-10.4 Unit on a scale Standard Deviation 21.33	-27.0 Unit on a scale Standard Deviation 30.58	1.1 Unit on a scale Standard Deviation 25.62

SECONDARY outcome

Timeframe: 18 months

Flare rate and time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18+ months

PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18+ months

PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

PD Cohort 2 (CFZ533): total soluble CD40 in plasma.

Outcome measures

Outcome data not reported

Adverse Events

VAY736 (Double-blind)

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

VAY736 Placebo (Double-blind)

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

CFZ533 (Double-blind)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

CFZ533 Placebo (Double-blind)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

All Patients (Double-blind)

Serious events: 6 serious events

Other events: 63 other events

Deaths: 0 deaths

VAY736/VAY736 (Open-label)

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

VAY736 Placebo/VAY736 (Open-label)

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

CFZ533/CFZ533 (Open-label)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

CFZ533 Placebo/CFZ533 (Open-label)

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

All Patients (Open-label)

Serious events: 11 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Measure	VAY736 (Double-blind) n=34 participants at risk VAY736 (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	VAY736 Placebo (Double-blind) n=33 participants at risk VAY736 Placebo (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	CFZ533 (Double-blind) n=20 participants at risk CFZ533 (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	CFZ533 Placebo (Double-blind) n=20 participants at risk CFZ533 Placebo (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	All Patients (Double-blind) n=107 participants at risk All patients in the blinded treatment phase	VAY736/VAY736 (Open-label) n=31 participants at risk VAY736/VAY736 (Open-label): Open-label period (Week 29 up to Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to the VAY736 arms	VAY736 Placebo/VAY736 (Open-label) n=31 participants at risk VAY736 Placebo/VAY736 (Open-label): Open-label period (Week 29 up to Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to VAY736 Placebo/VAY736 arms	CFZ533/CFZ533 (Open-label) n=20 participants at risk CFZ533/CFZ533 (Open-label): Open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to CFZ533 arms)	CFZ533 Placebo/CFZ533 (Open-label) n=16 participants at risk CFZ533 Placebo/CFZ533 (Open-label): Open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to CFZ533 Placebo/CFZ533 arms.	All Patients (Open-label) n=98 participants at risk All patients in the open-label treatment phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Nervous system disorders Central nervous system vasculitis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Nervous system disorders Syncope	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Cardiac disorders Acute myocardial infarction	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Ear and labyrinth disorders Vertigo positional	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Pancreatitis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Herpes zoster	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pneumonia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pneumonia bacterial	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pneumonia cytomegaloviral	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pyelonephritis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Salmonella bacteraemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Head injury	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Renal and urinary disorders Renal impairment	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.

Other adverse events

Measure	VAY736 (Double-blind) n=34 participants at risk VAY736 (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	VAY736 Placebo (Double-blind) n=33 participants at risk VAY736 Placebo (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	CFZ533 (Double-blind) n=20 participants at risk CFZ533 (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	CFZ533 Placebo (Double-blind) n=20 participants at risk CFZ533 Placebo (Double-blind): Double-blind treatment period (from first dose of study treatment until Week 25)	All Patients (Double-blind) n=107 participants at risk All patients in the blinded treatment phase	VAY736/VAY736 (Open-label) n=31 participants at risk VAY736/VAY736 (Open-label): Open-label period (Week 29 up to Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to the VAY736 arms	VAY736 Placebo/VAY736 (Open-label) n=31 participants at risk VAY736 Placebo/VAY736 (Open-label): Open-label period (Week 29 up to Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to VAY736 Placebo/VAY736 arms	CFZ533/CFZ533 (Open-label) n=20 participants at risk CFZ533/CFZ533 (Open-label): Open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to CFZ533 arms)	CFZ533 Placebo/CFZ533 (Open-label) n=16 participants at risk CFZ533 Placebo/CFZ533 (Open-label): Open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date, for participants randomized to CFZ533 Placebo/CFZ533 arms.	All Patients (Open-label) n=98 participants at risk All patients in the open-label treatment phase
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Blood and lymphatic system disorders Anaemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Blood and lymphatic system disorders Leukopenia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	4.1% 4/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Blood and lymphatic system disorders Neutropenia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 2/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Ear and labyrinth disorders Vertigo	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	12.5% 2/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Eye disorders Cataract	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Eye disorders Dry eye	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	12.5% 2/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Abdominal pain	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Diarrhoea	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 2/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	4.7% 5/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Dyspepsia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Gastrointestinal disorders Nausea	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
General disorders Injection site reaction	26.5% 9/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	9.3% 10/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	19.4% 6/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	35.5% 11/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	17.3% 17/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
General disorders Pyrexia	5.9% 2/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.7% 4/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Bacteraemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Bronchitis	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 2/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations COVID-19	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	12.9% 4/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 6/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Cellulitis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Cystitis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Gastroenteritis	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	9.7% 3/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.1% 5/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Herpes zoster	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Nasopharyngitis	20.6% 7/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	21.2% 7/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	15.0% 3/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	15.0% 3/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	18.7% 20/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	16.1% 5/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	25.0% 5/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	18.8% 3/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	15.3% 15/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Oral candidiasis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Oral fungal infection	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Oral herpes	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Pharyngitis	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Upper respiratory tract infection	8.8% 3/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 7/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Infections and infestations Urinary tract infection	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 2/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	4.7% 5/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Injection related reaction	5.9% 2/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	4.1% 4/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Investigations Blood immunoglobulin M decreased	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Investigations Cytomegalovirus test positive	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Metabolism and nutrition disorders Hypertriglyceridaemia	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 2/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Metabolism and nutrition disorders Hyperuricaemia	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Musculoskeletal and connective tissue disorders Back pain	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.8% 3/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.1% 3/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Nervous system disorders Dizziness	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.7% 4/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Nervous system disorders Headache	5.9% 2/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.0% 1/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	25.0% 5/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	8.4% 9/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	3.2% 1/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.5% 2/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.1% 6/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Psychiatric disorders Insomnia	2.9% 1/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.93% 1/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	9.7% 3/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.1% 5/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Skin and subcutaneous tissue disorders Acne	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	5.0% 1/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	2.0% 2/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	10.0% 2/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Skin and subcutaneous tissue disorders Leukoplakia	0.00% 0/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	6.2% 1/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.0% 1/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.
Vascular disorders Hypertension	5.9% 2/34 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/33 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	1.9% 2/107 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/31 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/20 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/16 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.	0.00% 0/98 • Treatment-emergent adverse events are presented for the double-blind treatment period (from first dose of study treatment until Week 25) and for the open-label period (Week 29 until Week 49), including AE in follow-up period up to the cut-off date. Any sign or symptom that occurred during the conduct of the trial and safety follow-up.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER