Trial Outcomes & Findings for Belimumab in Remission of VASculitis (NCT NCT01663623)

Last Updated: 2018-04-17

Results Overview

Time to relapse is defined as the number of days from Day 0 until the participant experienced a relapse (relapse date - treatment start date +1). Only post-baseline relapses were considered in these analyses. Only relapses occurring up to and including the last visit date in the double-blind treatment period were considered in these analyses. Intent-to-treat population comprised of all randomized participants who received at least one dose of study agent (belimumab or placebo). NA indicates that the data was not available as the Number of events is too low to estimate the value. Median and Inter-quartile range were presented and were based on Kaplan Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

106 participants

Primary outcome timeframe

Approximately up to 4 years

Results posted on

2018-04-17

Participant Flow

Participants with diagnosis of Granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were randomized in this study. The study was conducted at 37 centers in 15 countries in North America, Central America, South America, Western Europe, Eastern Europe, and Australia during 20 March 2013 - 06 February 2017.

A total of 164 participants were screened and 106 were enrolled and randomized in a 1:1 ratio to receive placebo or belimumab 10 milligram per kilogram (mg/kg). Of which, 105 received at least 1 dose of study agent and one participant was randomized in error.

Participant milestones

Participant milestones
Measure	Placebo Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Overall Study STARTED	52	53
Overall Study COMPLETED	40	33
Overall Study NOT COMPLETED	12	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Overall Study Adverse Event	3	7
Overall Study Lack of Efficacy	5	6
Overall Study Protocol Violation	0	1
Overall Study Other-Study closed/terminated	1	1
Overall Study Physician Decision	1	4
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Belimumab in Remission of VASculitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=52 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg n=53 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.	Total n=105 Participants Total of all reporting groups
Age, Continuous	53.5 Years STANDARD_DEVIATION 13.56 • n=5 Participants	56.2 Years STANDARD_DEVIATION 13.59 • n=7 Participants	54.8 Years STANDARD_DEVIATION 13.58 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	44 Participants n=5 Participants	46 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately up to 4 years

Population: Intent-to-treat population

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg n=53 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Time to First Relapse	NA Days Interval 789.0 to Kaplan Meier statistics could not be estimated where the number of events is too low. Hence it is NA.	NA Days Kaplan Meier statistics could not be estimated where the number of events is too low. Hence it is NA.

SECONDARY outcome

Timeframe: Approximately up to 4 years

Population: Intent-to-treat population

Data for number of participants with major relapse \[defined as experiencing at least 1 major Birmingham Vasculitis Activity Score (BVAS) item\] during the double-bind phase of the study was reported. Analysis was performed using a Cox proportional hazard model.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg n=53 Participants Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Number of Participants With Major Relapse During the Double-blind Phase of the Study	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 33 other events

Deaths: 0 deaths

Belimumab 10 mg/kg

Serious events: 18 serious events

Other events: 32 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo n=52 participants at risk Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg n=53 participants at risk Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Infections and infestations Bronchitis	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Cellulitis	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Influenza	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Lower respiratory tract infection	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Neutropenic sepsis	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Pyelonephritis acute	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Salmonellosis	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Tuberculosis	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Injury, poisoning and procedural complications Pneumothorax traumatic	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Injury, poisoning and procedural complications Post procedural discharge	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Injury, poisoning and procedural complications Tendon rupture	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Blood and lymphatic system disorders Anaemia	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Blood and lymphatic system disorders Neutropenia	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Blood and lymphatic system disorders Pancytopenia	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
General disorders Pyrexia	3.8% 2/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
General disorders General physical health deterioration	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Immune system disorders Hypersensitivity	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	3.8% 2/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Immune system disorders Anaphylactic reaction	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anal cancer	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Chronic gastritis	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Colitis ulcerative	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Hepatobiliary disorders Cholangitis	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Hepatobiliary disorders Drug-induced liver injury	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Musculoskeletal and connective tissue disorders Muscle contracture	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Nervous system disorders Haemorrhagic stroke	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Nervous system disorders Ischaemic stroke	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Cardiac disorders Sinus bradycardia	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Eye disorders Idiopathic orbital inflammation	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Investigations Liver function test increased	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Renal and urinary disorders Acute kidney injury	0.00% 0/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Vascular disorders Vasculitis	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.

Other adverse events
Measure	Placebo n=52 participants at risk Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	Belimumab 10 mg/kg n=53 participants at risk Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
Infections and infestations Nasopharyngitis	19.2% 10/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	11.3% 6/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Upper respiratory tract infection	15.4% 8/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	13.2% 7/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Urinary tract infection	7.7% 4/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Bronchitis	11.5% 6/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Influenza	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Infections and infestations Gastroenteritis	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	0.00% 0/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Nausea	3.8% 2/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	13.2% 7/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Diarrhoea	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Abdominal pain upper	7.7% 4/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	5.7% 3/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Vomiting	1.9% 1/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Gastrointestinal disorders Abdominal pain	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	1.9% 1/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Cough	15.4% 8/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	18.9% 10/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.8% 2/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	7.5% 4/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Musculoskeletal and connective tissue disorders Arthralgia	11.5% 6/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	11.3% 6/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Musculoskeletal and connective tissue disorders Back pain	7.7% 4/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	5.7% 3/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Musculoskeletal and connective tissue disorders Bursitis	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	3.8% 2/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
General disorders Fatigue	13.5% 7/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	13.2% 7/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
General disorders Pyrexia	3.8% 2/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	11.3% 6/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Nervous system disorders Headache	13.5% 7/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Skin and subcutaneous tissue disorders Rash	5.8% 3/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	9.4% 5/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.
Vascular disorders Hypertension	7.7% 4/52 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.	5.7% 3/53 • Adverse events (AE) were collected from the start of study agent administration (Day 0) through 8 weeks following administration of the last dose of study agent (approximately up to 4 years). Intent to treat population. Participants who discontinued treatment, all AE were collected through 8 weeks following the last dose of study agent. All SAEs were collected until relapse or the study was analyzed for the primary endpoint and study sites are informed that SAE data collection can cease, whichever occurs first.