A Study to Evaluate Avacopan in Participants With ANCA-associated Vasculitis
- Conditions
- Antineutrophil Cytoplasmic Antibody-associated Vasculitis
- Interventions
- Registration Number
- NCT06072482
- Lead Sponsor
- Amgen
- Brief Summary
The primary objective of this study is to evaluate the long-term safety of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Participants has provided informed consent before initiation of any study-specific activities/procedures.
- Newly diagnosed or relapse of granulomatosis with polyangiitis or microscopic polyangiitis, consistent with Chapel-Hill Consensus Conference definitions (Jennette et al, 2013), where induction treatment with cyclophosphamide or rituximab is needed.
- Age >/= 18 years (or >/= legal age within the country if it is older than 18 years).
- Positive test for anti-positive antiproteinase 3 or antimyeloperoxidase (current or historic) antibodies.
- At least 1 Birmingham Vasculitis Activity Score (BVAS) major item, or at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria.
- eGFR >/= 15 mL/min/1.73 m^2 (using Chronic Kidney Disease Epidemiology Collaboration equations).
Exclusion Criteria
- Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period of the study.
- Any other known multisystem autoimmune disease including eosinophilic granulomatosis with polyangiitis (GPA [Churg-Strauss]), systemic lupus erythematosus, immunoglobulin (Ig) A vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjogren's syndrome, anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis.
- Any medical condition requiring or expected to require continued use of immunosuppressive therapies, including corticosteroids that may cause confoundment with study assessments and study conclusions.
- Received dialysis or plasma exchange within 12 weeks before signing of the informed consent.
- Have had a kidney transplant.
- Malignancy (except curatively treated nonmelanoma skin cancers, curatively treated cervical carcinoma in situ, or breast ductal carcinoma in situ within the last 5 years before signing the informed consent).
- Acute or chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening.
- Positive test for active or latent tuberculosis during screening.
- White blood cell count < 3500/µL, neutrophil count < 1500/µL, or lymphocyte count < 500/µl. Note: Complete Blood Count can be repeated once in the screening period per investigator discretion. In this case, eligibility will be determined based on the repeat complete blood count.
- Evidence of clinically significant hepatic disease including prior diagnosis of cirrhosis.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >2.0 times the upper limit of normal (ULN).
- Total bilirubin > 1.5 times the ULN. A participant with documented Gilbert's syndrome with total bilirubin < 2 x ULN may be eligible.
- Active infection and/or infection requiring oral or intravenous (IV) anti-infective agents within 4 weeks before signing of the informed consent or completion of oral anti-infective agents within 2 weeks prior to signing informed consent.
- History of any clinically significant cardiovascular disease, such as symptomatic congestive heart failure, unstable angina, myocardial infarction or stroke, within 12 weeks before signing of the informed consent.
- Received cyclophosphamide (CYC) within 12 weeks before signing the informed consent; if on azathioprine (AZA), mycophenolate, or methotrexate at the time of screening, these drugs must be withdrawn before receiving the CYC or rituximab (RTX). Note: If induction therapy with cyclophosphamide was started within 1 week before signing the informed consent for the current episode of newly diagnosed or relapse of GPA or MPA, the participant may be eligible, provided no cyclophosphamide was received within 12 weeks before the start of the current induction therapy and if on AZA, mycophenolate, or MTX, these were withdrawn prior to receiving the current induction therapy with cyclophosphamide.
- Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone equivalent for more than 6 weeks continuously before signing of the informed consent.
- Received RTX or other B-cell depleting therapies within 26 weeks before signing of the informed consent. Note: If induction therapy with rituximab was started within 1 week before signing the informed consent for the current episode of newly diagnosed or relapse of GPA or MPA, the participant may be eligible, provided no rituximab was received within 26 weeks before the start of the current induction therapy and if on AZA, mycophenolate, or MTX, these were withdrawn prior to receiving the current induction therapy with RTX.
- Received any of the following within 12 weeks before signing the informed consent:
- antitumor necrosis factor treatment
- abatacept
- alemtuzumab
- IV Ig
- belimumab
- tocilizumab.
- Taking a strong or moderate inducer of the cytochrome P450 3A4 (CYP3A4) enzyme unless the strong or moderate CYP3A4 inducer can be changed to an alternative medicine at least 1 week before Day 1.
- Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) before signing of the informed consent.
- Previously received avacopan without clinical benefit per the Investigator's opinion or received avacopan within 60 days before signing of the informed consent.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B: Avacopan/Placebo + SoC Standard of Care Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy. Group A: Avacopan + Standard of Care (SoC) Standard of Care Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy. Group B: Avacopan/Placebo + SoC Placebo Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy. Group C: Placebo + SoC Standard of Care Placebo twice daily for 5 years + SoC background immunosuppressive therapy. Group C: Placebo + SoC Placebo Placebo twice daily for 5 years + SoC background immunosuppressive therapy. Group A: Avacopan + Standard of Care (SoC) Avacopan Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy. Group B: Avacopan/Placebo + SoC Avacopan Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Adverse Events Leading to Withdrawal Up to Month 60 Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Up to Month 60 Percentage of Participants Experiencing Adverse Events of Special Interest Up to Month 60 Number of Participants Experiencing Clinical Significant Changes from Baseline in Hematology Assessments Up to Month 60 Number of Participants Experiencing Clinical Significant Changes from Baseline in Serum Chemistry Assessments Up to Month 60 Number of Participants Experiencing Clinical Significant Changes from Baseline in Urinalysis Assessments Up to Month 60 Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements Up to Month 60 Percentage of Participants Experiencing Serious Adverse Events Up to Month 60 Percentage of Participants Experiencing Adverse Events Leading to Death Up to Month 60
- Secondary Outcome Measures
Name Time Method Group A and B Participants who Achieved Remission at Month 12: Time to Relapse in AAV Between Month 12 and Month 60 Month 12 to Month 60 Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12 Month 12 to Month 60 Groups A and C: Percentage of Participants who Achieved Sustained Remission at Month 60 Month 60 Group A and C Participants with Overt Renal Disease at Baseline: Change from Baseline to Month 60 in Estimated Glomerular Filtration Rate (eGFR) Baseline and Month 60 Groups A and C: Change from Baseline to Month 60 in Short Form 36 Health Survey Version 2 (SF-36 v2) General Health Perception Score Baseline and Month 60 Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Baseline and Month 60 Percentage of Participants who Achieved Remission at Month 6 Month 6 Groups A and C: Change from Baseline to Month 60 in Vasculitis Damage Index (VDI) Baseline and Month 60 Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death Up to Month 60 Percentage of Participants With Glucocorticoid Use Up to Month 60 Percentage of Participants With Immunosuppressant Use Up to Month 60
Trial Locations
- Locations (39)
Orthopedic Physicians Alaska
🇺🇸Anchorage, Alaska, United States
Scottsdale Healthcare at Shea - HonorHealth
🇺🇸Scottsdale, Arizona, United States
Southwest Kidney Institute
🇺🇸Surprise, Arizona, United States
Medvin Clinical Research
🇺🇸Menifee, California, United States
Palo Alto Medical Foundation Fremont
🇺🇸Fremont, California, United States
The Nephrology Group
🇺🇸Fresno, California, United States
Providence Medical Foundation
🇺🇸Fullerton, California, United States
Harbor University of California at Los Angeles Medical Center
🇺🇸Torrance, California, United States
Florida Kidney Physicians
🇺🇸Boca Raton, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Lake Cumberland Rheumatology
🇺🇸New Albany, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Dunes Clinical Research LLC
🇺🇸Sioux City, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Johns Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Womens Hospital
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Renown Rheumatology
🇺🇸Reno, Nevada, United States
New York Nephrology Vasculitis and Glomerular Center
🇺🇸Albany, New York, United States
Northwell Health
🇺🇸Great Neck, New York, United States
Hospital For Special Surgery
🇺🇸New York, New York, United States
East Carolina University Brody Outpatient Center
🇺🇸Greenville, North Carolina, United States
Brookview Hills Research Associates Llc
🇺🇸Winston-Salem, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Stat Research
🇺🇸Miamisburg, Ohio, United States
Hightower Clinical
🇺🇸Oklahoma City, Oklahoma, United States
Allegheny Health Network Cancer Institute at Mellon Pavilion
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Nephrology Associates Inc
🇺🇸East Providence, Rhode Island, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
West Tennessee Physicians' Alliance - Arthritis Clinic
🇺🇸Jackson, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Renal Disease Research Institute - Landry Office
🇺🇸Dallas, Texas, United States
Nephrology Associates of Northern Virginia Inc
🇺🇸Fairfax, Virginia, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Rheumatology and Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States