Clinical trial NCT06072482: A Study to Evaluate Avacopan in Participants With ANCA-associated Vasculitis
Official title: A Randomized, Double-blind, Placebo-controlled Phase 4 Clinical Trial to Evaluate the Long-term Safety and Efficacy of Avacopan in Participants With Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Antineutrophil Cytoplasmic Antibody-associated Vasculitis
Keywords: Avacopan
ANCA-associated Vasculitis
AAV
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-10-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Month 60
measure: Percentage of Participants Experiencing Adverse Events of Special Interest
timeFrame: Up to Month 60
measure: Percentage of Participants Experiencing Serious Adverse Events
timeFrame: Up to Month 60
measure: Percentage of Participants Experiencing Adverse Events Leading to Withdrawal
timeFrame: Up to Month 60
measure: Percentage of Participants Experiencing Adverse Events Leading to Death
timeFrame: Up to Month 60
measure: Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements
timeFrame: Up to Month 60
measure: Number of Participants Experiencing Clinical Significant Changes from Baseline in Hematology Assessments
timeFrame: Up to Month 60
measure: Number of Participants Experiencing Clinical Significant Changes from Baseline in Serum Chemistry Assessments
timeFrame: Up to Month 60
measure: Number of Participants Experiencing Clinical Significant Changes from Baseline in Urinalysis Assessments
timeFrame: Up to Month 60
Secondary outcomes:
measure: Group A and B Participants who Achieved Remission at Month 12: Time to Relapse in AAV Between Month 12 and Month 60
timeFrame: Month 12 to Month 60
measure: Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12
timeFrame: Month 12 to Month 60
measure: Groups A and C: Percentage of Participants who Achieved Sustained Remission at Month 60
timeFrame: Month 60
measure: Group A and C Participants with Overt Renal Disease at Baseline: Change from Baseline to Month 60 in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and Month 60
measure: 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
timeFrame: Baseline and Month 60
measure: Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
timeFrame: Baseline and Month 60
measure: Percentage of Participants who Achieved Remission at Month 6
timeFrame: Month 6
measure: Groups A and C: Change from Baseline to Month 60 in Vasculitis Damage Index (VDI)
timeFrame: Baseline and Month 60
measure: Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death
timeFrame: Up to Month 60
measure: Percentage of Participants With Glucocorticoid Use
timeFrame: Up to Month 60
measure: Percentage of Participants With Immunosuppressant Use
timeFrame: Up to Month 60
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Orthopedic Physicians Alaska
state: Alaska
city: Scottsdale
country: United States
facility: Scottsdale Healthcare at Shea - HonorHealth
state: Arizona
city: Surprise
country: United States
facility: Southwest Kidney Institute
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Fremont
country: United States
facility: Palo Alto Medical Foundation Fremont
state: California
city: Fresno
country: United States
facility: The Nephrology Group
state: California
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Menifee
country: United States
facility: Medvin Clinical Research
state: California
city: Torrance
country: United States
facility: Harbor University of California at Los Angeles Medical Center
state: California
city: Boca Raton
country: United States
facility: Florida Kidney Physicians
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: New Albany
country: United States
facility: Lake Cumberland Rheumatology
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Sioux City
country: United States
facility: Dunes Clinical Research LLC
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Reno
country: United States
facility: Renown Rheumatology
state: Nevada
city: Albany
country: United States
facility: New York Nephrology Vasculitis and Glomerular Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: Greenville
country: United States
facility: East Carolina University Brody Outpatient Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates Llc
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Miamisburg
country: United States
facility: Stat Research
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allegheny Health Network Cancer Institute at Mellon Pavilion
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: East Providence
country: United States
facility: Nephrology Associates Inc
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Jackson
country: United States
facility: West Tennessee Physicians' Alliance - Arthritis Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Renal Disease Research Institute - Landry Office
state: Texas
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia Inc
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Beckley
country: United States
facility: Rheumatology and Pulmonary Clinic
state: West Virginia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: