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

Purpose

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).

Condition

  • Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group A: Avacopan + Standard of Care (SoC) 		Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.
  • Drug: Avacopan
    Administered orally.
    Other names:
    • CCX168
  • Drug: Standard of Care
    All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.
Experimental
Group B: Avacopan/Placebo + SoC 		Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
  • Drug: Avacopan
    Administered orally.
    Other names:
    • CCX168
  • Drug: Placebo
    Administered orally.
  • Drug: Standard of Care
    All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.
Placebo Comparator
Group C: Placebo + SoC 		Placebo twice daily for 5 years + SoC background immunosuppressive therapy.
  • Drug: Placebo
    Administered orally.
  • Drug: Standard of Care
    All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com