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Belimumab in Remission of VASculitis (BREVAS)

Primary Purpose

Vasculitis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Belimumab 10 mg/kg
Azathioprine
Sponsored by
Human Genome Sciences Inc., a GSK Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vasculitis focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • GSK Investigational Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo plus azathioprine

Belimumab 10 mg/kg plus azathioprine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
August 9, 2012
Last Updated
March 15, 2018
Sponsor
Human Genome Sciences Inc., a GSK Company
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01663623
Brief Title
Belimumab in Remission of VASculitis
Acronym
BREVAS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 20, 2013 (Actual)
Primary Completion Date
February 6, 2017 (Actual)
Study Completion Date
February 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Human Genome Sciences Inc., a GSK Company
Collaborators
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vasculitis
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo plus azathioprine
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Belimumab 10 mg/kg plus azathioprine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Intervention Type
Biological
Intervention Name(s)
Belimumab 10 mg/kg
Other Intervention Name(s)
BENLYSTA™
Intervention Description
Belimumab 10 mg/kg
Intervention Type
Drug
Intervention Name(s)
Azathioprine
Intervention Description
Azathioprine
Primary Outcome Measure Information:
Title
Time to First Relapse
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants With Major Relapse During the Double-blind Phase of the Study
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
GSK Investigational Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36693
Country
United States
Facility Name
GSK Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
GSK Investigational Site
City
Covina
State/Province
California
ZIP/Postal Code
91723
Country
United States
Facility Name
GSK Investigational Site
City
Palo Alto
State/Province
California
ZIP/Postal Code
94030
Country
United States
Facility Name
GSK Investigational Site
City
San Leandro
State/Province
California
ZIP/Postal Code
94578
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
GSK Investigational Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118-2307
Country
United States
Facility Name
GSK Investigational Site
City
West Springfield
State/Province
Massachusetts
ZIP/Postal Code
1089
Country
United States
Facility Name
GSK Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
GSK Investigational Site
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103-1438
Country
United States
Facility Name
GSK Investigational Site
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43203
Country
United States
Facility Name
GSK Investigational Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
GSK Investigational Site
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
GSK Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
GSK Investigational Site
City
Garran
State/Province
Australian Capital Territory
ZIP/Postal Code
2605
Country
Australia
Facility Name
GSK Investigational Site
City
New Lambton
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Facility Name
GSK Investigational Site
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
GSK Investigational Site
City
Liverpool
ZIP/Postal Code
2107
Country
Australia
Facility Name
GSK Investigational Site
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
GSK Investigational Site
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
GSK Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GSK Investigational Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3L9
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
GSK Investigational Site
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
GSK Investigational Site
City
Praha 2
ZIP/Postal Code
12850
Country
Czechia
Facility Name
GSK Investigational Site
City
Praha 4
ZIP/Postal Code
14021
Country
Czechia
Facility Name
GSK Investigational Site
City
Lille cedex
ZIP/Postal Code
59037
Country
France
Facility Name
GSK Investigational Site
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
GSK Investigational Site
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
GSK Investigational Site
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
GSK Investigational Site
City
Stuttgart
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
70376
Country
Germany
Facility Name
GSK Investigational Site
City
Tuebingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
GSK Investigational Site
City
Muenster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Facility Name
GSK Investigational Site
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
GSK Investigational Site
City
Jena
State/Province
Thueringen
ZIP/Postal Code
07740
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
GSK Investigational Site
City
Kirchheim unter Teck
ZIP/Postal Code
73230
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
GSK Investigational Site
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
GSK Investigational Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
GSK Investigational Site
City
Dublin
ZIP/Postal Code
4
Country
Ireland
Facility Name
GSK Investigational Site
City
Dublin
ZIP/Postal Code
9
Country
Ireland
Facility Name
GSK Investigational Site
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
GSK Investigational Site
City
Torrette Di Ancona
State/Province
Marche
ZIP/Postal Code
60126
Country
Italy
Facility Name
GSK Investigational Site
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
GSK Investigational Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
ZIP/Postal Code
20153
Country
Italy
Facility Name
GSK Investigational Site
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
GSK Investigational Site
City
Mexico
ZIP/Postal Code
7760
Country
Mexico
Facility Name
GSK Investigational Site
City
Kristiansand
ZIP/Postal Code
4604
Country
Norway
Facility Name
GSK Investigational Site
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Facility Name
GSK Investigational Site
City
Callao
ZIP/Postal Code
Callao 2
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima 21
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima 27
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima 31
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima 36
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima 41
Country
Peru
Facility Name
GSK Investigational Site
City
Lima
ZIP/Postal Code
Lima14
Country
Peru
Facility Name
GSK Investigational Site
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
GSK Investigational Site
City
Katowice
ZIP/Postal Code
40-635
Country
Poland
Facility Name
GSK Investigational Site
City
Krakow
ZIP/Postal Code
31-066
Country
Poland
Facility Name
GSK Investigational Site
City
Lublin
ZIP/Postal Code
20-954
Country
Poland
Facility Name
GSK Investigational Site
City
Bucharest
ZIP/Postal Code
020125
Country
Romania
Facility Name
GSK Investigational Site
City
Cluj-Napoca
ZIP/Postal Code
400006
Country
Romania
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
119992
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Saint-Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Stavropol
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
GSK Investigational Site
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
GSK Investigational Site
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
GSK Investigational Site
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
GSK Investigational Site
City
Zuerich
ZIP/Postal Code
8006
Country
Switzerland
Facility Name
GSK Investigational Site
City
Reading
State/Province
Berkshire
ZIP/Postal Code
RG1 5AN
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Aberdeen
ZIP/Postal Code
AB25 2ZD
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Oxford
ZIP/Postal Code
OX3 7LD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30666823
Citation
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.
Results Reference
derived

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Belimumab in Remission of VASculitis

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