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NCT06072482PHASE4Recruiting

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

Amgen

Start Date

2/7/2024

Completion Date

12/31/2036

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

Age Range: 18 years to 100 years

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 that may confound study assessments and study conclusions including but not limited to 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 other 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 16 weeks before Day 1 randomization. * 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 Day 1 randomization. * Acute or chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening. * Any known exposure to a case of active tuberculosis (TB) within the last 12 weeks before Day 1 randomization. * Positive test for active or latent TB 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 at the investigator discretion. In such instances, 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. Note: A participant with documented Gilbert's syndrome with total bilirubin \< 2 x ULN may be eligible. * Any of the following within 6 weeks prior to Day 1 randomization: serious infection, infection requiring treatment with intravenous (IV) anti-infective agents, any other infection (including active infection, chronic infection, opportunistic infection, or history of recurrent infection) that in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion. Oral or vaginal candidiasis and cutaneous or nail fungal infections do not constitute an exclusion. * Any of the following within 12 weeks prior to Day 1 randomization: myocardial infarction, stroke, unstable angina, symptomatic congestive heart failure requiring prescription medication, any other clinically significant cardiovascular disease that in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion. * Received cyclophosphamide (CYC) within 12 weeks before signing the informed consent; if on azathioprine (AZA), mycophenolate, or methotrexate (MTX) at the time of screening, these drugs must be withdrawn before receiving CYC. Note: If induction therapy with CYC was started within 1 week before signing the informed consent for the current episode of newly diagnosed or relapse of GPA or microscopic polyangiitis (MPA), the participant may be eligible, provided no CYC 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 CYC. * 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; if on AZA, mycophenolate, or MTX at the time of screening, these drugs must be withdrawn before receiving rituximab (RTX). Note: If induction therapy with RTX 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 RTX 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 16 weeks before Day 1 randomization: * antitumor necrosis factor treatment * abatacept * alemtuzumab * IV Ig * belimumab * anti interleukin-6 agent (eg, tocilizumab, sarilumab). * 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 randomization. * Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) before Day 1 randomization. * Previously received avacopan without clinical benefit per the Investigator's opinion or received avacopan within 60 days before Day 1 randomization.

Interventions

DRUG

Avacopan

DRUG

Placebo

DRUG

Standard of Care

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Conditions

Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Locations

Orthopedic Physicians Alaska

Anchorage, Alaska 99508

United States

Scottsdale Healthcare at Shea - HonorHealth

Scottsdale, Arizona 85258

United States

Southwest Kidney Institute

Surprise, Arizona 85374

United States

Unity Health

Searcy, Arkansas 72143

United States

Medvin Clinical Research

Covina, California 91722

United States

Palo Alto Medical Foundation Fremont

Fremont, California 94538

United States

The Nephrology Group

Fresno, California 93720

United States

Providence Medical Foundation

Fullerton, California 92835

United States

Southland Arthritis and Osteoarthritis Medical Center, Inc

Menifee, California 92586

United States

University of California San Francisco- Zuckerburg San Francisco General

San Francisco, California 94110

United States

Harbor University of California at Los Angeles Medical Center

Torrance, California 90502

United States

Amicis Research Center

Valencia, California 91355

United States

University of Colorado

Aurora, Colorado 80045

United States

Florida Kidney Physicians

Boca Raton, Florida 33431

United States

Malcom Randall Veterans Affairs Medical Center

Gainesville, Florida 32608

United States

Mayo Clinic

Jacksonville, Florida 32224

United States

ClinTrial Research Oakwater, Llc

Orlando, Florida 32806

United States

University of South Florida

Tampa, Florida 33606

United States

Emory University

Atlanta, Georgia 30322

United States

Lake Cumberland Rheumatology

New Albany, Indiana 47150

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa 52242

United States

Dunes Clinical Research LLC

Sioux City, Iowa 51104

United States

University of Kentucky

Lexington, Kentucky 40536

United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland 21224

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Brigham and Womens Hospital

Boston, Massachusetts 02115

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Kidney Michigan Institute

Saginaw, Michigan 49804

United States

Clinical Research Institute of Michigan

Saint Clair Shores, Michigan 48081

United States

Revive Research Institute

Sterling Heights, Michigan 48313

United States

University of Minnesota

Minneapolis, Minnesota 55414

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Renown Rheumatology

Reno, Nevada 89502

United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire 03766

United States

Renal Medicine Associates

Albuquerque, New Mexico 87109

United States

New York Nephrology Vasculitis and Glomerular Center

Albany, New York 12209

United States

Northwell Health

Great Neck, New York 11021

United States

Hospital For Special Surgery

New York, New York 10021

United States

Carolina Kidney Associates

Greensboro, North Carolina 27405

United States

East Carolina University Brody Outpatient Center

Greenville, North Carolina 27834

United States

Brookview Hills Research Associates Llc

Winston-Salem, North Carolina 27103

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

The Ohio State University

Columbus, Ohio 43201

United States

Stat Research

Miamisburg, Ohio 45342

United States

Hightower Clinical

Oklahoma City, Oklahoma 73114

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15213

United States

Allegheny Health Network Cancer Institute at Mellon Pavilion

Pittsburgh, Pennsylvania 15224

United States

Nephrology Associates Inc

East Providence, Rhode Island 02914

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Carolina Nephrology PA

Spartanburg, South Carolina 29306

United States

West Tennessee Research Institute

Jackson, Tennessee 38305

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

Vital Rheumatology

Austin, Texas 78727

United States

Renal Disease Research Institute - Landry Office

Dallas, Texas 75204

United States

Epic Medical Research - Red Oak

Red Oak, Texas 75154

United States

Scott and White Memorial Hospital

Temple, Texas 76502

United States

Nephrology Associates of Northern Virginia Inc

Fairfax, Virginia 22033

United States

Virginia Mason Medical Center

Seattle, Washington 98101

United States

Rheumatology and Pulmonary Clinic

Beckley, West Virginia 25801

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05

Czechia

Fakultni nemocnice Olomouc

Olomouc, 779 00

Czechia

Fakultni nemocnice Ostrava

Ostrava - Poruba, 708 52

Czechia

Fakultni nemocnice Plzen

Pilsen, 304 60

Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, 100 34

Czechia

Revmatologicky ustav

Prague, 128 00

Czechia

Vseobecna fakultni nemocnice v Praze

Prague, 128 08

Czechia

Aalborg Universitetshospital

Aalborg, 9000

Denmark

Rigshospitalet

Copenhagen, 2100

Denmark

Odense Universitetshospital

Odense C, 5000

Denmark

General Hospital of Athens Laiko

Athens, 11527

Greece

Hippokration General Hospital of Athens

Athens, 11527

Greece

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032

Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7632

Hungary

SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi

Lodz, 90-153

Poland

Spzoz Centralny Szpital Kliniczny Umed w Lodzi

Lodz, 92-213

Poland

Narodowy Instytut Geriatrii Reumatologii i Rehabilitacji im prof dr hab med Eleonory Reicher

Warsaw, 02-637

Poland

Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy Centralny Szpital Kliniczny Mon

Warsaw, 04-141

Poland

Spitalul Clinic Sf Maria, Bucuresti

Bucharest, 011172

Romania

Spitalul Clinic Dr Ion Cantacuzino

Bucharest, 020475

Romania

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, 400006

Romania