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

Amgen

Status and phase: Enrolling; Phase 4

Conditions: Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Treatments: Drug: Avacopan; Drug: Standard of Care; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06072482

EU CT Number (Other Identifier)

20220159

Details and patient eligibility

About

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).

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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300 participants in 3 patient groups, including a placebo group

Group A: Avacopan + Standard of Care (SoC)

Experimental group

Description:

Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.

Treatment:

Drug: Standard of Care

Drug: Avacopan

Group B: Avacopan/Placebo + SoC

Experimental group

Description:

Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.

Treatment:

Drug: Placebo

Drug: Standard of Care

Drug: Avacopan

Group C: Placebo + SoC

Placebo Comparator group

Description:

Placebo twice daily for 5 years + SoC background immunosuppressive therapy.

Treatment:

Drug: Placebo

Drug: Standard of Care