Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's)

NCT02108860 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: ABROGATE 55272013-005535-24U54AR057319
• Study Type: interventional
• Target: 65
• Locations: 5 countries
• Sites: 20

Brief Summary

Multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of abatacept to achieve sustained glucocorticoid-free remission in patients with relapsing non-severe granulomatosis with polyangiitis (Wegener's) (GPA) . Participants will be randomized 1:1 to receive either abatacept 125 mg or placebo administered by subcutaneous injection once a week. Participants will continue on study treatment for a minimum of 12 months unless they experience a disease relapse or disease flare. Participants who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 6 will have the option of entering an open-label trial period whereby they would receive open-label abatacept.

Conditions

Granulomatosis With Polyangiitis (Wegener's); Granulomatosis With Polyangiitis; Wegener's Granulomatosis; ANCA-Associated Vasculitis

Keywords

Granulomatosis with polyangiitis (Wegener's); Granulomatosis with polyangiitis; GPA; Wegener's granulomatosis; Wegener granulomatosis; Anti Neutrophil Cytoplasmic Antibody Associated Vasculitis; ANCA Associated Vasculitis; AAV; Vasculitis; Systemic vasculitis; Systemic inflammatory disease; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Abatacept; CTLA4-Ig; Immunosuppressive agent; Prednisone; Glucocorticoids; Glucocorticoid; Corticosteroid; Corticosteroids; Treatment; Pharmacologic Actions; Therapeutic Uses; Anti Inflammatory Agents

Outcome Measures

Primary Outcomes (1)

• Ability of abatacept to reduce the treatment failure rate

  Treatment failure will be defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 or 1 by 6 months. Relapse will be defined as any of the following after remission: an increase in BVAS/WG, development of a new BVAS/WG item, or symptoms/signs of GPA that cannot be attributed to any cause other than GPA and that requires institution or dosage increase of prednisone. Disease worsening will be defined as any of the following prior to remission: an increase in BVAS/WG, development of a new BVAS/WG item, or symptoms/signs of GPA that cannot be attributed to any cause other than GPA and that requires institution or dosage increase of prednisone.

  12 months

Secondary Outcomes (5)

• Duration of glucocorticoid-free periods

  12 months

• Severity of relapses in those treated with abatacept versus placebo

  12 months

• Health-related quality of life in those treated with abatacept versus placebo

  12 months

• Prevention of disease- or treatment-related damage with abatacept versus placebo

  12 months

• Safety of abatacept in GPA

  12 months

Study Arms (2)

Blinded abatacept

EXPERIMENTAL

Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission by treatment month 6.

Drug: Abatacept

blinded placebo

PLACEBO COMPARATOR

Participants will receive blinded placebo. Placebo will be administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission by treatment month 6.

Drug: placebo

Interventions

Abatacept DRUG

Those randomized to abatacept will receive abatacept 125 mg administered by subcutaneous injection once a week Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 6 will have the option of entering an open-label trial period whereby they would receive open-label abatacept. .

Also known as: CTLA4-Ig, Orencia

Blinded abatacept

placebo DRUG

Those randomized to placebo will receive a sterile placebo solution administered by subcutaneous injection once a week.

blinded placebo

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be considered as being best characterized as GPA and not microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) and must have met at least 2 of the 5 modified ACR classification criteria for GPA. These do not need to be present at the time of study entry. The modified ACR criteria are:
• Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
• Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities
• Active urinary sediment, defined as microscopic hematuria (\>5 red blood cells per high power field) or red blood cell casts
• Granulomatous inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area (artery or arteriole)
• Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 or myeloperoxidase measured by enzyme-linked immunoassay
• Relapse of GPA within the 28 days prior to screening where the active disease features meet the following definition of non-severe disease:
• No disease manifestations that would be scored as a major element in the BVAS/WG
• Absence of any disease feature that poses an immediate threat to either a critical individual organ or the patient's life
• Age 15 and older
• Willing and able to comply with treatment and follow-up procedures
• Both women and men must be willing to use an effective means of birth control while receiving treatment through this study. Women should continue the use of an effective means of birth control for a minimum of 14 weeks after the last dose of study drug. Effective contraception methods include abstinence, oral contraceptives (birth control pills), IUD, diaphragm, Norplant, approved hormone injections, condoms, or medical sterilization. If applicable, participating sites will defer to their local authorities if they require stricter guidelines on the types of allowable contraception methods.
• Willing and able to provide written informed consent (and written assent of minor participants if applicable.)

You may not qualify if:

• Presence of involvement that does not meet the criteria for non-severe disease
• Treatment with CYC within 3 months prior to screening
• Treatment with methylprednisolone 1000 mg within 28 days prior to enrollment
• Treatment with prednisone or prednisolone\> 30 mg/day for \> 28 days immediately prior to study entry
• Initiation or dose increase of the maintenance immunosuppressive agent (MTX, AZA, MA) within 3 months prior to screening
• Evidence of active infection (includes chronic infection)
• Patients who are pregnant or who are nursing
• Known infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen
• Inability to comply with study guidelines
• Cytopenia: platelet count \< 100,000/mm3, white blood cell count (WBC) \< 3,000/mm3 (3 x 109/L), absolute neutrophil count \< 1500/mm3, hemoglobin (Hgb) \< 8.5 g/dL
• Chronic renal insufficiency defined by a creatinine clearance of less than or equal to 20 ml/min
• AST or ALT \> 3 times above the upper limit of the normal laboratory range
• Known current use of illegal drugs
• Other uncontrolled disease (co-morbidity) that could prevent a patient from fulfilling the study requirements or that would substantially increase the risk of study procedures
• History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure

Sponsors & Collaborators

• University of South Florida: lead
• The Cleveland Clinic: collaborator
• Bristol-Myers Squibb: collaborator
• University of Pennsylvania: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (20)

Cedars Sinai Medical Center, Los Angeles

Los Angeles, California, 90048, United States

Location

University of South Florida Rheumatology

Tampa, Florida, 33612, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

University of Calgary

Calgary, Alberta, T3M 1M4, Canada

Location

University of British Columbia, St. Paul's Rheumatology Clinic

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

St. Joseph's Hospital, Hamilton

Hamilton, Ontario, Canada

Location

Mount Sinai Hospital, Toronto

Toronto, Ontario, M5T 3L9, Canada

Location

Medius Kliniken

Kirchheim unter Teck, 73230, Germany

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

University of Aberdeen

Aberdeen, AB25 2ZD, United Kingdom

Location

University of Cambridge- Addenbrookes Hospital

Cambridge, United Kingdom

Location

Nottingham University Hospitals

Nottingham, NG7 2UH, United Kingdom

Location

Royal Berkshire Hospital

Reading, RG1 5AN, United Kingdom

Location

Related Publications (1)

• Hung W, Cusnir I, Habib S, Smylie M, Solez K, Yacyshyn E. Immune checkpoint inhibitor-induced granulomatosis with polyangiitis. Rheumatology (Oxford). 2021 Jun 18;60(6):e190-e191. doi: 10.1093/rheumatology/keaa818. No abstract available.

  PMID: 33367837 DERIVED

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis; Systemic Vasculitis; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Carol A Langford, MD, MHS

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Jeffrey P Krischer, PhD

  University of South Florida

  PRINCIPAL INVESTIGATOR

• Peter A Merkel, MD, MPH

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 9, 2014
• Study Start: April 25, 2015
• Primary Completion: July 25, 2023
• Study Completion: December 20, 2023
• Last Updated: July 29, 2024

Record last verified: 2024-07

Locations

DE (1); IE (1); US (10); CA (4); GB (4)