Belimumab in Remission of VASculitis (BREVAS)

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

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.

Study Overview

• Status: Completed
• Conditions: Vasculitis
• Intervention / Treatment: Biological: Placebo; Drug: Azathioprine; Biological: Belimumab 10 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Liverpool, Australia, 2107
    • GSK Investigational Site
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • GSK Investigational Site
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • GSK Investigational Site
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • GSK Investigational Site
• Belgium
  • Brussels, Belgium, 1090
    • GSK Investigational Site
  • Bruxelles, Belgium, 1020
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5T 3L9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H1T 2M4
      • GSK Investigational Site
• Czechia
  • Praha 2, Czechia, 12850
    • GSK Investigational Site
  • Praha 2, Czechia, 12808
    • GSK Investigational Site
  • Praha 4, Czechia, 14021
    • GSK Investigational Site
• France
  • Lille cedex, France, 59037
    • GSK Investigational Site
  • Paris, France, 75014
    • GSK Investigational Site
  • Pessac, France, 33604
    • GSK Investigational Site
  • Rennes, France, 35033
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Kirchheim unter Teck, Germany, 73230
    • GSK Investigational Site
  • Muenchen, Germany, 80336
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Stuttgart, Baden-Wuerttemberg, Germany, 70376
      • GSK Investigational Site
    • Tuebingen, Baden-Wuerttemberg, Germany, 72076
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07740
      • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1023
    • GSK Investigational Site
  • Debrecen, Hungary, 4032
    • GSK Investigational Site
• Ireland
  • Dublin, Ireland, 9
    • GSK Investigational Site
  • Dublin, Ireland, 4
    • GSK Investigational Site
• Italy
  • Bari, Italy, 70124
    • GSK Investigational Site
  • Bologna, Italy, 40138
    • GSK Investigational Site
  • Milano, Italy, 20153
    • GSK Investigational Site
  • Reggio Emilia, Italy, 42100
    • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Marche
    • Torrette Di Ancona, Marche, Italy, 60126
      • GSK Investigational Site
• Mexico
  • Mexico, Mexico, 7760
    • GSK Investigational Site
• Norway
  • Kristiansand, Norway, 4604
    • GSK Investigational Site
  • Oslo, Norway, 0372
    • GSK Investigational Site
• Peru
  • Callao, Peru, Callao 2
    • GSK Investigational Site
  • Lima, Peru, Lima 27
    • GSK Investigational Site
  • Lima, Peru, Lima 41
    • GSK Investigational Site
  • Lima, Peru, Lima 31
    • GSK Investigational Site
  • Lima, Peru, Lima 21
    • GSK Investigational Site
  • Lima, Peru, Lima 36
    • GSK Investigational Site
  • Lima, Peru, Lima14
    • GSK Investigational Site
• Poland
  • Gdansk, Poland, 80-952
    • GSK Investigational Site
  • Katowice, Poland, 40-635
    • GSK Investigational Site
  • Krakow, Poland, 31-066
    • GSK Investigational Site
  • Lublin, Poland, 20-954
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400006
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 119992
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 190068
    • GSK Investigational Site
  • Stavropol, Russian Federation
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08025
    • GSK Investigational Site
  • Barcelona, Spain, 8036
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
• Sweden
  • Stockholm, Sweden, 14186
    • GSK Investigational Site
• Switzerland
  • Bern, Switzerland, 3010
    • GSK Investigational Site
  • St. Gallen, Switzerland, 9007
    • GSK Investigational Site
  • Zuerich, Switzerland, 8006
    • GSK Investigational Site
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZD
    • GSK Investigational Site
  • Cambridge, United Kingdom, CB2 0QQ
    • GSK Investigational Site
  • London, United Kingdom, SE1 7EH
    • GSK Investigational Site
  • Oxford, United Kingdom, OX3 7LD
    • GSK Investigational Site
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG1 5AN
      • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • GSK Investigational Site
    • Mobile, Alabama, United States, 36693
      • GSK Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85724
      • GSK Investigational Site
  • California
    • Covina, California, United States, 91723
      • GSK Investigational Site
    • Palo Alto, California, United States, 94030
      • GSK Investigational Site
    • San Leandro, California, United States, 94578
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • GSK Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2307
      • GSK Investigational Site
    • West Springfield, Massachusetts, United States, 1089
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • GSK Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • GSK Investigational Site
  • New Jersey
    • Camden, New Jersey, United States, 08103-1438
      • GSK Investigational Site
  • New York
    • Great Neck, New York, United States, 11021
      • GSK Investigational Site
    • New York, New York, United States, 10021
      • GSK Investigational Site
    • New York, New York, United States, 10016
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • GSK Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15261
      • GSK Investigational Site
    • Wyomissing, Pennsylvania, United States, 19610
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus azathioprine; 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; Placebo; Drug: Azathioprine; Azathioprine
Experimental: Belimumab 10 mg/kg plus azathioprine; 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.	Drug: Azathioprine; Azathioprine; Biological: Belimumab 10 mg/kg; Belimumab 10 mg/kg; Other Names: BENLYSTA™

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc., a GSK Company
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Jayne D, Blockmans D, Luqmani R, Moiseev S, Ji B, Green Y, Hall L, Roth D, Henderson RB, Merkel PA; BREVAS Study Collaborators. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol. 2019 Jun;71(6):952-963. doi: 10.1002/art.40802. Epub 2019 Apr 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2013
• Primary Completion (Actual): February 6, 2017
• Study Completion (Actual): February 6, 2017

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: March 15, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Autoimmune Diseases; Granulomatosis with polyangiitis; Vasculitis; Belimumab; MPA; GPA; ANCA; WG; Wegener's Granulomatosis; Microscopic Polyangiitis; Systemic Vasculitis; anti-MPO; anti-proteinase 3; anti-neutrophil cytoplasmic antibody; anti-myeloperoxidase; anti-PR3
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Cerebral Small Vessel Diseases; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis; Microscopic Polyangiitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Azathioprine; Belimumab
• Other Study ID Numbers: 115466

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No