Belimumab in Remission of VASculitis

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Multi-Center, Multinational, Randomized, Double-Blind, Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) in Combination With Azathioprine for the Maintenance of Remission in Wegener's Granulomatosis and Microscopic Polyangiitis

Conditions
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Vasculitis

Intervention / Treatment
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* Biological: Placebo
* Biological: Belimumab 10 mg/kg
* Drug: Azathioprine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo plus azathioprine<br>Placebo IV plus oral azathioprine 2 mg/kg/day; placebo administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to receive treatment with belimumab in a 6-month open-label extension phase. Placebo patients who opt to participate in the extension will receive belimumab 10 mg/kg IV every 28 days plus oral azathioprine 2 mg/kg/day for an additional 6 months. | Biological: Placebo<br>* Placebo<br>Drug: Azathioprine<br>* Azathioprine<br>|
| Experimental: Belimumab 10 mg/kg plus azathioprine<br>Belimumab 10 mg/kg IV plus oral azathioprine 2 mg/kg/day; belimumab administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to continue treatment with belimumab in a 6-month open-label extension phase. Patients who opt to participate in the extension will continue to receive belimumab 10 mg/kg IV every 28 plus oral azathioprine 2 mg/kg/day days for an additional 6 months. | Biological: Belimumab 10 mg/kg<br>* Belimumab 10 mg/kg<br>* Other names: BENLYSTA™;Drug: Azathioprine<br>* Azathioprine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Approximately up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Approximately up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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