Belimumab in Remission of VASculitis

NCT01663623 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 115466
• Study Type: interventional
• Target: 106
• Locations: 20 countries
• Sites: 89

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Participants With Major Relapse During the Double-blind Phase of the Study

  Approximately up to 4 years

Study Arms (2)

Placebo plus azathioprine

PLACEBO COMPARATOR

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; Drug: Azathioprine

Belimumab 10 mg/kg plus azathioprine

EXPERIMENTAL

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; Drug: Azathioprine

Interventions

Placebo BIOLOGICAL

Placebo

Placebo plus azathioprine

Belimumab 10 mg/kg BIOLOGICAL

Belimumab 10 mg/kg

Also known as: BENLYSTA™

Belimumab 10 mg/kg plus azathioprine

Azathioprine DRUG

Azathioprine

Belimumab 10 mg/kg plus azathioprine; Placebo plus azathioprine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Human Genome Sciences Inc., a GSK Company: lead
• GlaxoSmithKline: collaborator

Study Sites (89)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

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GSK Investigational Site

Mobile, Alabama, 36693, United States

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Tucson, Arizona, 85724, United States

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GSK Investigational Site

Covina, California, 91723, United States

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Palo Alto, California, 94030, United States

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GSK Investigational Site

San Leandro, California, 94578, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

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GSK Investigational Site

Kansas City, Kansas, 66160, United States

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GSK Investigational Site

Boston, Massachusetts, 02118-2307, United States

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GSK Investigational Site

West Springfield, Massachusetts, 1089, United States

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GSK Investigational Site

Detroit, Michigan, 48202, United States

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Rochester, Minnesota, 55905, United States

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GSK Investigational Site

Camden, New Jersey, 08103-1438, United States

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GSK Investigational Site

Great Neck, New York, 11021, United States

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GSK Investigational Site

New York, New York, 10016, United States

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GSK Investigational Site

New York, New York, 10021, United States

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Columbus, Ohio, 43203, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15261, United States

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Wyomissing, Pennsylvania, 19610, United States

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Milwaukee, Wisconsin, 53226, United States

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Garran, Australian Capital Territory, 2605, Australia

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New Lambton, New South Wales, 2305, Australia

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Malvern, Victoria, 3144, Australia

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Liverpool, 2107, Australia

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Brussels, 1020, Belgium

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Brussels, 1090, Belgium

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Leuven, 3000, Belgium

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GSK Investigational Site

Hamilton, Ontario, L8N 4A6, Canada

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Toronto, Ontario, M5T 3L9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Prague, 12808, Czechia

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Prague, 12850, Czechia

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GSK Investigational Site

Prague, 14021, Czechia

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GSK Investigational Site

Lille, 59037, France

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Paris, 75014, France

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GSK Investigational Site

Pessac, 33604, France

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Rennes, 35033, France

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70376, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

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GSK Investigational Site

Leipzig, Saxony, 04103, Germany

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GSK Investigational Site

Jena, Thuringia, 07740, Germany

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GSK Investigational Site

Berlin, 10117, Germany

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GSK Investigational Site

Kirchheim unter Teck, 73230, Germany

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München, 80336, Germany

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Budapest, 1023, Hungary

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Debrecen, 4032, Hungary

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GSK Investigational Site

Dublin, 4, Ireland

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Dublin, 9, Ireland

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Genoa, Liguria, 16132, Italy

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GSK Investigational Site

Torrette Di Ancona, The Marches, 60126, Italy

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Bari, 70124, Italy

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Bologna, 40138, Italy

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Milan, 20153, Italy

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GSK Investigational Site

Reggio Emilia, 42100, Italy

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GSK Investigational Site

México, 7760, Mexico

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Kristiansand, 4604, Norway

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Oslo, 0372, Norway

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GSK Investigational Site

Callao, Callao 2, Peru

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Lima, Lima 21, Peru

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Lima, Lima 27, Peru

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GSK Investigational Site

Lima, Lima 31, Peru

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GSK Investigational Site

Lima, Lima 36, Peru

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GSK Investigational Site

Lima, Lima 41, Peru

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GSK Investigational Site

Lima, Lima14, Peru

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GSK Investigational Site

Gdansk, 80-952, Poland

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GSK Investigational Site

Katowice, 40-635, Poland

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Krakow, 31-066, Poland

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GSK Investigational Site

Lublin, 20-954, Poland

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GSK Investigational Site

Bucharest, 020125, Romania

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GSK Investigational Site

Cluj-Napoca, 400006, Romania

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GSK Investigational Site

Moscow, 119992, Russia

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GSK Investigational Site

Saint Petersburg, 190068, Russia

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GSK Investigational Site

Stavropol, Russia

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GSK Investigational Site

Barcelona, 08025, Spain

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GSK Investigational Site

Barcelona, 8036, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Stockholm, 14186, Sweden

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GSK Investigational Site

Bern, 3010, Switzerland

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GSK Investigational Site

Sankt Gallen, 9007, Switzerland

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GSK Investigational Site

Zurich, 8006, Switzerland

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GSK Investigational Site

Reading, Berkshire, RG1 5AN, United Kingdom

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GSK Investigational Site

Aberdeen, AB25 2ZD, United Kingdom

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GSK Investigational Site

Cambridge, CB2 0QQ, United Kingdom

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GSK Investigational Site

London, SE1 7EH, United Kingdom

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GSK Investigational Site

Oxford, OX3 7LD, United Kingdom

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Related Publications (1)

• 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.

  PMID: 30666823 DERIVED

MeSH Terms

Conditions

Vasculitis; Granulomatosis with Polyangiitis; Autoimmune Diseases; Microscopic Polyangiitis; Systemic Vasculitis

Interventions

belimumab; Azathioprine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The sample size was small as it was truncated from approximately 300 to 100 participants, largely owing to a change in standard of care.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2012
• First Posted: August 13, 2012
• Study Start: March 20, 2013
• Primary Completion: February 6, 2017
• Study Completion: February 6, 2017
• Last Updated: April 17, 2018
• Results First Posted: April 17, 2018

Record last verified: 2018-03

Locations

CZ (3); AU (4); CA (4); CH (3); RO (2); US (22); RU (3); ES (3); PL (4); IT (6); FR (4); DE (8); NO (2); ME (1); SE (1); BE (3); GB (5); HU (2); IE (2); PE (7)