A Study to Evaluate Avacopan in Participants With ANCA-associated Vasculitis

• Status: Recruiting
• Trial end date: 2031-08-05
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen

Criteria

Inclusion Criteria:

• 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 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, 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 (Churg-Strauss), systemic lupus erythematosus, immunoglobulin 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 nonmelanoma skin cancers, cervical 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.

• Evidence of clinically significant hepatic disease including prior diagnosis of cirrhosis.

• aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >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) antimicrobials within 4 weeks before signing of the 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, mycophenolate, or methotrexate at the time of screening, these drugs must be withdrawn before receiving the CYC or rituximab (RTX).

• 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 52 weeks before signing of the informed consent or within 26 weeks before signing of the informed consent provided CD19 count > 0.01x10^9/L, or received any of the following within 12 weeks before signing the informed consent:

• antitumor necrosis factor treatment

• abatacept

• alemtuzumab

• IV immunoglobulin

• 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.