A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
ADVOCATE
A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine
2 other identifiers
interventional
331
19 countries
183
Brief Summary
The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2017
Typical duration for phase_3
183 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2016
CompletedFirst Posted
Study publicly available on registry
December 16, 2016
CompletedStudy Start
First participant enrolled
March 15, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 7, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2019
CompletedResults Posted
Study results publicly available
September 9, 2022
CompletedMarch 24, 2025
March 1, 2025
2.5 years
December 11, 2016
May 19, 2022
March 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Subjects Achieving Disease Remission at Week 26
Disease remission at Week 26 was defined as: * Achieving a BVAS of 0 as determined by the Adjudication Committee; * No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26; * No BVAS \>0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment).
Week 26
Percentage of Subjects Achieving Sustained Disease Remission at Week 52
Sustained remission at Week 52 was defined as: * Disease remission at Week 26 as defined above; * Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52; * No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee.
Week 52
Secondary Outcomes (26)
Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs
From day 1 throughout the study period (day 421/week 60)
Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI
Baseline, Week 13 and 26
Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC
Week 4
Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index
Baseline, Week 26 and 52
Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study
Week 52
- +21 more secondary outcomes
Study Arms (2)
Prednisone group
ACTIVE COMPARATORAvacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.
Avacopan group
EXPERIMENTALAvacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Interventions
Avacopan 30 mg twice daily orally for 52 weeks (364 days): \- Three 10 mg avacopan capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone-matching placebo tapering regimen over 20 weeks (140 days): * Prednisone-matching placebo capsules equivalent to 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was \<55 kg, starting on Day 1 with tapering according to a protocol-specified schedule. * Adolescents who weighed ≤37 kg started at a prednisone-matching placebo dose of 30 mg per day.
Avacopan-matching placebo twice daily orally for 52 weeks (364 days): \- Three avacopan-matching placebo capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone tapering regimen over 20 weeks (140 days): * Prednisone 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was \<55 kg, starting on Day 1 with tapering according to the protocol-specified schedule. * Adolescents who weighed ≤37 kg started at a prednisone dose of 30 mg per day.
Eligibility Criteria
You may qualify if:
- Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis
- Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed associated vasculitis (AAV) where treatment with cyclophosphamide or rituximab is needed; where approved by Regulatory Agencies, adolescents (12-17 year old) may be enrolled
- Use of adequate contraception
- Positive test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO)
- At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS)
- Estimated glomerular filtration rate ≥15 mL/minute/1.73 m\^2 at screening
You may not qualify if:
- Pregnant or breast-feeding
- Alveolar hemorrhage requiring pulmonary ventilation support at screening
- Any other known multi-system autoimmune disease
- Required dialysis or plasma exchange within 12 weeks prior to screening
- Have a kidney transplant
- Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
- Received intravenous glucocorticoids, \>3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
- Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening
- Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., CD19 count \> 0.01x10\^9/L); received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening
- For patients scheduled to receive cyclophosphamide treatment, urinary outflow obstruction, active infection (especially varicella zoster infection), or platelet count \<50,000/μL before start of dosing
- Participated previously in a CCX168 study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (198)
Clinical Trial Site
Huntsville, Alabama, 35801, United States
Clinical Trial Site
Phoenix, Arizona, 85012, United States
Clinical Trial Site
Phoenix, Arizona, 85032, United States
Clinical Trial Site
Los Angeles, California, 90048, United States
Clinical Trial Site
Santa Monica, California, 90404, United States
Clinical Trial Site
Aurora, Colorado, 80045, United States
Clinical Trial Site
Washington D.C., District of Columbia, 20007, United States
Clinical Trial Site
Daytona Beach, Florida, 32117, United States
Clinical Trial Site
Tampa, Florida, 33612, United States
Clinical Trial Site
Atlanta, Georgia, 30322, United States
Clinical Trial Site
Meridian, Idaho, 83605, United States
Clinical Trial Site
Chicago, Illinois, 60637, United States
Clinical Trial Site
Indianapolis, Indiana, 46202, United States
Clinical Trial Site
Kansas City, Kansas, 66160, United States
Clinical Trial Site
Lexington, Kentucky, 40536, United States
Clinical Trial Site
Shreveport, Louisiana, 71101, United States
Clinical Trial Site
Baltimore, Maryland, 21224, United States
Clinical Trial Site
Boston, Massachusetts, 02114, United States
Clinical Trial Site
Boston, Massachusetts, 02118, United States
Clinical Trial Site
Ann Arbor, Michigan, 48109, United States
Clinical Trial Site
Minneapolis, Minnesota, 55414, United States
Clinical Trial Site
Rochester, Minnesota, 55905, United States
Clinical Trial Site
St Louis, Missouri, 63110, United States
Clinical Trial Site
Great Neck, New York, 11021, United States
Clinical Trial Site
Mineola, New York, 11501, United States
Clinical Trial Site
New York, New York, 10021, United States
Clinical Trial Site
New York, New York, 10032, United States
Clinical Trial Site
Chapel Hill, North Carolina, 27599, United States
Clinical Trial Site
Greenville, North Carolina, 27834, United States
Clinical Trial Site
Winston-Salem, North Carolina, 27103, United States
Clinical Trial Site
Cleveland, Ohio, 44195, United States
Clinical Trial Site
Columbus, Ohio, 43210, United States
Clinical Trial Site
Duncansville, Pennsylvania, 16635, United States
Clinical Trial Site
Philadelphia, Pennsylvania, 19104, United States
Clinical Trial Site
Pittsburgh, Pennsylvania, 15225, United States
Clinical Trial Site
Providence, Rhode Island, 02903, United States
Clinical Trial Site
Charleston, South Carolina, 29406, United States
Clinical Trial Site
Dallas, Texas, 75235, United States
Clinical Trial Site
Houston, Texas, 77030, United States
Clinical Trial Site
Salt Lake City, Utah, 84132, United States
Clinical Trial Site
Seattle, Washington, 98101, United States
Clinical Trial Site
Adelaide, Australia
Clinical Trial Site
Auchenflower, Australia
Clinical Trial Site
Brisbane, Australia
Clinical Trial Site
Clayton, Australia
Clinical Trial Site
Concord, Australia
Clinical Trial Site
Heidelberg, Australia
Clinical Trial Site
Liverpool, Australia
Clinical Trial Site
Nambour, Australia
Clinical Trial Site
Nedlands, Australia
Clinical Trial Site
Randwick, Australia
Clinical Trial Site
Saint Albans, Australia
Clinical Trial Site
Southport, Australia
Clinical Trial Site
St Leonards, Australia
Clinical Trial Site
Westmead, Australia
Clinical Trial Site
Woolloongabba, Australia
Clinical Trial Site
Feldkirch, Austria
Clinical Trial Site
Graz, Austria
Clinical Trial Site
Innsbruck, Austria
Clinical Trial Site
Antwerp, Belgium
Clinical Trial Site
Brussels, Belgium
Clinical Trial Site
Leuven, Belgium
Clinical Trial Site
Liège, Belgium
Clinical Trial Site
Calgary, Canada
Clinical Trial Site
Greenfield Park, Canada
Clinical Trial Site
Hamilton, Canada
Clinical Trial Site
Montreal, Canada
Clinical Trial Site
Québec, Canada
Clinical Trial Site
Sherbrooke, Canada
Clinical Trial Site
Toronto, Canada
Clinical Trial Site
Vancouver, Canada
Clinical Trial Site
Olomouc, Czechia
Clinical Trial Site
Prague, Czechia
Clinical Trial Site
Aalborg, Denmark
Clinical Trial Site
Aarhus, Denmark
Clinical Trial Site
Copenhagen, Denmark
Clinical Trial Site
Odense, Denmark
Clinical Trial Site
Roskilde, Denmark
Clinical Trial Site
Angers, France
Clinical Trial Site
Bordeaux, France
Clinical Trial Site
Boulogne-sur-Mer, France
Clinical Trial Site
Brest, France
Clinical Trial Site
Bron, France
Clinical Trial Site
Caen, France
Clinical Trial Site
Colmar, France
Clinical Trial Site
Grenoble, France
Clinical Trial Site
Marseille, France
Clinical Trial Site
Metz, France
Clinical Trial Site
Nantes, France
Clinical Trial Site
Nîmes, France
Clinical Trial Site
Paris, France
Clinical Trial Site
Toulouse, France
Clinical Trial Site
Valenciennes, France
Clinical Trial Site
Aachen, Germany
Clinical Trial Site
Bad Bramstedt, Germany
Clinical Trial Site
Berlin, Germany
Clinical Trial Site
Cologne, Germany
Clinical Trial Site
Dresden, Germany
Clinical Trial Site
Essen, Germany
Clinical Trial Site
Freiburg im Breisgau, Germany
Clinical Trial Site
Fulda, Germany
Clinical Trial Site
Hamburg, Germany
Clinical Trial Site
Hanover, Germany
Clinical Trial Site
Heidelberg, Germany
Clinical Trial Site
Jena, Germany
Clinical Trial Site
Kirchheim unter Teck, Germany
Clinical Trial Site
Leipzig, Germany
Clinical Trial Site
Ludwigshafen, Germany
Clinical Trial Site
Lübeck, Germany
Clinical Trial Site
Mannheim, Germany
Clinical Trial Site
Munich, Germany
Clinical Trial Site
Tübingen, Germany
Clinical Trial Site
Villingen-Schwenningen, Germany
Clinical Trial Site
Budapest, Hungary
Clinical Trial Site
Debrecen, Hungary
Clinical Trial Site
Cork, Ireland
Clinical Trial Site
Dublin, Ireland
Clinical Trial Site
Ancona, Italy
Clinical Trial Site
Florence, Italy
Clinical Trial Site
Genova, Italy
Clinical Trial Site
Milan, Italy
Clinical Trial Site
Monza, Italy
Clinical Trial Site
Parma, Italy
Clinical Trial Site
Reggio Emilia, Italy
Clinical Trial Site
Torino, Italy
Clinical Trial Site
Udine, Italy
Clinical Trial Site
Aichi, Japan
Clinical Trial Site
Akita, Japan
Clinical Trial Site
Chiba, Japan
Clinical Trial Site
Hiroshima, Japan
Clinical Trial Site
Hokkaido, Japan
Clinical Trial Site
Ishikawa, Japan
Clinical Trial Site
Kagawa, Japan
Clinical Trial Site
Kanagawa, Japan
Clinical Trial Site
Kobe, Japan
Clinical Trial Site
Miyazaki, Japan
Clinical Trial Site
Nagoya, Japan
Clinical Trial Site
Okayama, Japan
Clinical Trial Site
Osaka, Japan
Clinical Trial Site
Saitama, Japan
Clinical Trial Site
Shimane, Japan
Clinical Trial Site
Shizuoka, Japan
Clinical Trial Site
Tokyo, Japan
Clinical Trial Site
Toyama, Japan
Clinical Trial Site
Yokohama, Japan
Clinical Trial Site
Groningen, Netherlands
Clinical Trial Site
Leiden, Netherlands
Clinical Trial Site
Rotterdam, Netherlands
Clinical Trial Site
Christchurch, New Zealand
Clinical Trial Site
Dunedin, New Zealand
Clinical Trial Site
Grafton, New Zealand
Clinical Trial Site
Hamilton, New Zealand
Clinical Trial Site
Takapuna, New Zealand
Clinical Trial Site
Nordbyhagen, Norway
Clinical Trial Site
Oslo, Norway
Clinical Trial Site
Tromsø, Norway
Clinical Trial Site
Badalona, Spain
Clinical Trial Site
Barcelona, Spain
Clinical Trial Site
Burela de Cabo, Spain
Clinical Trial Site
Lleida, Spain
Clinical Trial Site
Madrid, Spain
Clinical Trial Site
San Sebastián, Spain
Clinical Trial Site
Linköping, Sweden
Clinical Trial Site
Lund, Sweden
Clinical Trial Site
Örebro, Sweden
Clinical Trial Site
Stockholm, Sweden
Clinical Trial Site
Uppsala, Sweden
Clinical Trial Site
Basel, Switzerland
Clinical Trial Site
Bern, Switzerland
Clinical Trial Site
Fribourg, Switzerland
Clinical Trial Site
Lausanne, Switzerland
Clinical Trial Site
Sankt Gallen, Switzerland
Clinical Trial Site
Zurich, Switzerland
Clinical Trial Site
Aberdeen, United Kingdom
Clinical Trial Site
Basildon, United Kingdom
Clinical Trial Site
Birmingham, United Kingdom
Clinical Trial Site
Bristol, United Kingdom
Clinical Trial Site
Cambridge, United Kingdom
Clinical Trial Site
Canterbury, United Kingdom
Clinical Trial Site
Cardiff, United Kingdom
Clinical Trial Site
Carshalton, United Kingdom
Clinical Trial Site
Dorchester, United Kingdom
Clinical Trial Site
Dudley, United Kingdom
Clinical Trial Site
Exeter, United Kingdom
Clinical Trial Site
Glasgow, United Kingdom
Clinical Trial Site
Inverness, United Kingdom
Clinical Trial Site
Kirkcaldy, United Kingdom
Clinical Trial Site
Leeds, United Kingdom
Clinical Trial Site
Leicester, United Kingdom
Clinical Trial Site
Liverpool, United Kingdom
Clinical Trial Site
London, United Kingdom
Clinical Trial Site
Manchester, United Kingdom
Clinical Trial Site
Newcastle, United Kingdom
Clinical Trial Site
Nottingham, United Kingdom
Clinical Trial Site
Oxford, United Kingdom
Clinical Trial Site
Reading, United Kingdom
Clinical Trial Site
Salford, United Kingdom
Clinical Trial Site
Westcliff-on-Sea, United Kingdom
Related Publications (5)
Geetha D, Neumann T, Karras A, Cid MC, Merkel PA, Bray S, Bozeman AM, Jayne DRW; Members of the ADVOCATE Study Group. Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide. RMD Open. 2025 Oct 5;11(4):e005743. doi: 10.1136/rmdopen-2025-005743.
PMID: 41052893DERIVEDGeetha D, Dua A, Yue H, Springer J, Salvarani C, Jayne D, Merkel P; ADVOCATE Study Group. Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial. Ann Rheum Dis. 2024 Jan 11;83(2):223-232. doi: 10.1136/ard-2023-224816.
PMID: 37979959DERIVEDSoulsby WD. Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". ACR Open Rheumatol. 2022 Jul;4(7):558-561. doi: 10.1002/acr2.11412. Epub 2022 Feb 15.
PMID: 35167187DERIVEDJayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386.
PMID: 33596356DERIVEDMerkel PA, Jayne DR, Wang C, Hillson J, Bekker P. Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial. JMIR Res Protoc. 2020 Apr 7;9(4):e16664. doi: 10.2196/16664.
PMID: 32088663DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical trial disclosure
- Organization
- ChemoCentryx, Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- This study was double-blind, double-dummy, i.e., placebo capsules were identical in appearance to the avacopan capsules, and prednisone capsules also had matching placebo capsules. To maintain the blind, multiple measures were taken (i.e., randomization code was not accessible to study personnel who had contact with study centers or who were involved in data management and analysis for the duration of the study).
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2016
First Posted
December 16, 2016
Study Start
March 15, 2017
Primary Completion
September 7, 2019
Study Completion
November 1, 2019
Last Updated
March 24, 2025
Results First Posted
September 9, 2022
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- 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 (or other new use) 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.
- 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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.
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request