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

A Randomized, Double-blind, Placebo-controlled Phase 4 Clinical Trial to Evaluate the Long-term Safety and Efficacy of Avacopan in Subjects With Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

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).

Study Overview

• Status: Recruiting
• Conditions: Antineutrophil Cytoplasmic Antibody-associated Vasculitis
• Intervention / Treatment: Drug: Placebo; Drug: Avacopan; Drug: Standard of Care

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Recruiting
      • Orthopedic Physicians Alaska
  • Arizona
    • Surprise, Arizona, United States, 85374
      • Recruiting
      • Southwest Kidney Institute
  • California
    • Covina, California, United States, 91722
      • Recruiting
      • Medvin Clinical Research
    • Fresno, California, United States, 93720
      • Recruiting
      • The Nephrology Group
    • Fullerton, California, United States, 92835
      • Recruiting
      • Providence Medical Foundation
    • Menifee, California, United States, 92586
      • Recruiting
      • Medvin Clinical Research
    • Torrance, California, United States, 90502
      • Recruiting
      • Harbor University of California at Los Angeles Medical Center
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Recruiting
      • Lake Cumberland Rheumatology
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • New York
    • Great Neck, New York, United States, 11021
      • Recruiting
      • Northwell Health
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • East Carolina University Brody Outpatient Center
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Brookview Hills Research Associates, llc
  • Ohio
    • Miamisburg, Ohio, United States, 45342
      • Recruiting
      • Stat Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Allegheny Health Network Cancer Institute at Mellon Pavilion
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Recruiting
      • Nephrology Associates Inc
  • Texas
    • Dallas, Texas, United States, 75204
      • Recruiting
      • Renal Disease Research Institute
  • Washington
    • Seattle, Washington, United States, 98101
      • Recruiting
      • Virginia Mason Medical Center
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Recruiting
      • Rheumatology and Pulmonary Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Placebo; Administered orally.; 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Percentage of Participants Experiencing Serious Adverse Events	Up to Month 60
Percentage of Participants Experiencing Adverse Events Leading to Withdrawal	Up to Month 60
Percentage of Participants Experiencing Adverse Events Leading to Death	Up to Month 60
Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements	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

Secondary Outcome Measures

Outcome Measure	Time Frame
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 Week 60 in Vasculitis Damage Index (VDI)	Baseline and Week 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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2024
• Primary Completion (Estimated): August 5, 2031
• Study Completion (Estimated): August 5, 2031

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: AAV; Avacopan; ANCA-associated Vasculitis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: 20220159; EU CT Number (Other Identifier: 2023-503184-42)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No