Vasculitis
Conditions
Keywords
Wegener's Granulomatosis, anti-MPO, WG, Belimumab, GPA, anti-proteinase 3, anti-neutrophil cytoplasmic antibody, anti-myeloperoxidase, Granulomatosis with polyangiitis, Vasculitis, Autoimmune Diseases, Microscopic Polyangiitis, anti-PR3, ANCA, MPA, Systemic Vasculitis
Brief summary
The purpose of this study is to evaluate the efficacy and safety of belimumab, in combination with azathioprine, for the maintenance of remission following a standard induction regimen in patients with Wegener's granulomatosis or microscopic polyangiitis. The random assignment in this study is 1 to 1 which means that participants have an equal chance of receiving belimumab or placebo.
Interventions
Sponsors
GlaxoSmithKline
Human Genome Sciences Inc., a GSK Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis Wegener's granulomatosis or microscopic polyangiitis by Chapel Hill criteria. * Disease flare in the past 26 weeks requiring treatment with high dose corticosteroids and 1 of the following medications: rituximab, oral cyclophosphamide OR IV cyclophosphamide. * Tested positive for anti-proteinase 3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies at any time prior to enrollment. * Achieve remission no more than 26 weeks after first dose of induction treatment. Remission is defined as a Birmingham Vasculitis Activity (BVAS) score of 0 and receiving less than 10 mg/day of oral prednisone (or equivalent) on 2 consecutive visits 21 to 35 days apart. * Maintenance therapy on this study must start no more than 2 weeks after confirmation of remission. Key
Exclusion criteria
* Pregnant or nursing. * Receipt of a B cell targeted therapy (other than rituximab) at anytime * Receipt of an investigational biological agent within the past 60 days. * Required management of acute or chronic infections within the past 60 days. * Current drug or alcohol abuse or dependence. * Current or past positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. * History of severe allergic reaction to contrast agents or biological medicines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Relapse | Approximately up to 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Relapse During the Double-blind Phase of the Study | Approximately up to 4 years | 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Ireland, Italy, Mexico, Norway, Peru, Poland, Romania, Russia, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 52 |
| 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. | 53 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 7 |
| Overall Study | Lack of Efficacy | 5 | 6 |
| Overall Study | Other-Study closed/terminated | 1 | 1 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Belimumab 10 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 53.5 Years STANDARD_DEVIATION 13.56 | 56.2 Years STANDARD_DEVIATION 13.59 | 54.8 Years STANDARD_DEVIATION 13.58 |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 5 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Central/South Asian Heritage | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 44 Participants | 46 Participants | 90 Participants |
| Sex: Female, Male Female | 25 Participants | 26 Participants | 51 Participants |
| Sex: Female, Male Male | 27 Participants | 27 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 1 / 53 |
| other Total, other adverse events | 33 / 52 | 32 / 53 |
| serious Total, serious adverse events | 16 / 52 | 18 / 53 |
Outcome results
Primary
Time to First Relapse
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.
Time frame: Approximately up to 4 years
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Relapse | NA Days |
| Belimumab 10 mg/kg | Time to First Relapse | NA Days |
p-value: 0.88495% CI: [0.44, 2.59]Cox Proportional Hazards model
Secondary
Number of Participants With Major Relapse During the Double-blind Phase of the Study
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.
Time frame: Approximately up to 4 years
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Major Relapse During the Double-blind Phase of the Study | 0 Participants |
| Belimumab 10 mg/kg | Number of Participants With Major Relapse During the Double-blind Phase of the Study | 1 Participants |