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

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.

Study Overview

• Status: Completed
• Conditions: ANCA-Associated Vasculitis
• Intervention / Treatment: Drug: Prednisone; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Azathioprine; Drug: Avacopan

Detailed Description

Complement 5a and its receptor C5aR (CD88) are involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

This is a randomized, double-blind, active-controlled Phase 3 study to evaluate the safety and efficacy of the orally-administered, selective C5aR inhibitor CCX168 (avacopan) in inducing and sustaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated concomitantly with Rituximab or Cyclophosphamide/Azathioprine.

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

• Study Type: Interventional
• Enrollment (Actual): 331
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • 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
• Austria
  • Feldkirch, Austria
    • Clinical Trial Site
  • Graz, Austria
    • Clinical Trial Site
  • Innsbruck, Austria
    • Clinical Trial Site
• Belgium
  • Antwerp, Belgium
    • Clinical Trial Site
  • Brussels, Belgium
    • Clinical Trial Site
  • Leuven, Belgium
    • Clinical Trial Site
  • Liège, Belgium
    • Clinical Trial Site
• Canada
  • Calgary, Canada
    • Clinical Trial Site
  • Greenfield Park, Canada
    • Clinical Trial Site
  • Hamilton, Canada
    • Clinical Trial Site
  • Montréal, Canada
    • Clinical Trial Site
  • Québec, Canada
    • Clinical Trial Site
  • Sherbrooke, Canada
    • Clinical Trial Site
  • Toronto, Canada
    • Clinical Trial Site
  • Vancouver, Canada
    • Clinical Trial Site
• Czechia
  • Olomouc, Czechia
    • Clinical Trial Site
  • Praha, Czechia
    • Clinical Trial Site
• Denmark
  • Aalborg, Denmark
    • Clinical Trial Site
  • Aarhus, Denmark
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  • Copenhagen, Denmark
    • Clinical Trial Site
  • Odense, Denmark
    • Clinical Trial Site
  • Roskilde, Denmark
    • Clinical Trial Site
• France
  • Angers, France
    • Clinical Trial Site
  • Bordeaux, France
    • Clinical Trial Site
  • Boulogne-sur-Mer, France
    • Clinical Trial Site
  • Brest, France
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  • Bron, France
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  • Caen, France
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  • Colmar, France
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  • Grenoble, France
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  • Marseille, France
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  • Metz, France
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  • Nantes, France
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  • Nîmes, France
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  • Paris, France
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  • Toulouse, France
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  • Valenciennes, France
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• Germany
  • Aachen, Germany
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  • Bad Bramstedt, Germany
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  • Berlin, Germany
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  • Cologne, Germany
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  • Dresden, Germany
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  • Essen, Germany
    • Clinical Trial Site
  • Freiburg, Germany
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  • Fulda, Germany
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  • Hamburg, Germany
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  • Hannover, Germany
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  • Heidelberg, Germany
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  • Jena, Germany
    • Clinical Trial Site
  • Kirchheim unter Teck, Germany
    • Clinical Trial Site
  • Leipzig, Germany
    • Clinical Trial Site
  • Ludwigshafen, Germany
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  • Lübeck, Germany
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  • Mannheim, Germany
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  • Munich, Germany
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  • Tuebingen, Germany
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  • Villingen-Schwenningen, Germany
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• Hungary
  • Budapest, Hungary
    • Clinical Trial Site
  • Debrecen, Hungary
    • Clinical Trial Site
• Ireland
  • Cork, Ireland
    • Clinical Trial Site
  • Dublin, Ireland
    • Clinical Trial Site
• Italy
  • Ancona, Italy
    • Clinical Trial Site
  • Firenze, Italy
    • Clinical Trial Site
  • Genova, Italy
    • Clinical Trial Site
  • Milano, Italy
    • Clinical Trial Site
  • Monza, Italy
    • Clinical Trial Site
  • Parma, Italy
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  • Reggio Emilia, Italy
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  • Torino, Italy
    • Clinical Trial Site
  • Udine, Italy
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• Japan
  • 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
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  • Tokyo, Japan
    • Clinical Trial Site
  • Toyama, Japan
    • Clinical Trial Site
  • Yokohama, Japan
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• Netherlands
  • Groningen, Netherlands
    • Clinical Trial Site
  • Leiden, Netherlands
    • Clinical Trial Site
  • Rotterdam, Netherlands
    • Clinical Trial Site
• New Zealand
  • 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
• Norway
  • Nordbyhagen, Norway
    • Clinical Trial Site
  • Oslo, Norway
    • Clinical Trial Site
  • Tromsø, Norway
    • Clinical Trial Site
• Spain
  • Badalona, Spain
    • Clinical Trial Site
  • Barcelona, Spain
    • Clinical Trial Site
  • Burela, Spain
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  • Lleida, Spain
    • Clinical Trial Site
  • Madrid, Spain
    • Clinical Trial Site
  • San Sebastián, Spain
    • Clinical Trial Site
• Sweden
  • Linköping, Sweden
    • Clinical Trial Site
  • Lund, Sweden
    • Clinical Trial Site
  • Stockholm, Sweden
    • Clinical Trial Site
  • Uppsala, Sweden
    • Clinical Trial Site
  • Örebro, Sweden
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• Switzerland
  • Basel, Switzerland
    • Clinical Trial Site
  • Bern, Switzerland
    • Clinical Trial Site
  • Fribourg, Switzerland
    • Clinical Trial Site
  • Lausanne, Switzerland
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  • St. Gallen, Switzerland
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  • Zürich, Switzerland
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• United Kingdom
  • Aberdeen, United Kingdom
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  • Basildon, United Kingdom
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  • Birmingham, United Kingdom
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  • Bristol, United Kingdom
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  • Cambridge, United Kingdom
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  • Canterbury, United Kingdom
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  • Cardiff, United Kingdom
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  • Carshalton, United Kingdom
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  • Dorchester, United Kingdom
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  • Dudley, United Kingdom
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  • Exeter, United Kingdom
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  • Glasgow, United Kingdom
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  • Inverness, United Kingdom
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  • Kirkcaldy, United Kingdom
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  • Leeds, United Kingdom
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  • Leicester, United Kingdom
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  • Liverpool, United Kingdom
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  • London, United Kingdom
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  • Manchester, United Kingdom
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  • Newcastle, United Kingdom
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  • Nottingham, United Kingdom
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  • Oxford, United Kingdom
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  • Reading, United Kingdom
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  • Salford, United Kingdom
    • Clinical Trial Site
  • Westcliff-on-Sea, United Kingdom
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• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Clinical Trial Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Clinical Trial Site
    • Phoenix, Arizona, United States, 85012
      • Clinical Trial Site
  • California
    • Los Angeles, California, United States, 90048
      • Clinical Trial Site
    • Santa Monica, California, United States, 90404
      • Clinical Trial Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Trial Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Clinical Trial Site
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Clinical Trial Site
    • Tampa, Florida, United States, 33612
      • Clinical Trial Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Clinical Trial Site
  • Idaho
    • Meridian, Idaho, United States, 83605
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Clinical Trial Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Clinical Trial Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Clinical Trial Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Clinical Trial Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Clinical Trial Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Clinical Trial Site
    • Boston, Massachusetts, United States, 02114
      • Clinical Trial Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Clinical Trial Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Clinical Trial Site
    • Rochester, Minnesota, United States, 55905
      • Clinical Trial Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Clinical Trial Site
  • New York
    • Great Neck, New York, United States, 11021
      • Clinical Trial Site
    • Mineola, New York, United States, 11501
      • Clinical Trial Site
    • New York, New York, United States, 10032
      • Clinical Trial Site
    • New York, New York, United States, 10021
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  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical Trial Site
    • Greenville, North Carolina, United States, 27834
      • Clinical Trial Site
    • Winston-Salem, North Carolina, United States, 27103
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  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Clinical Trial Site
    • Columbus, Ohio, United States, 43210
      • Clinical Trial Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Clinical Trial Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical Trial Site
    • Pittsburgh, Pennsylvania, United States, 15225
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  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Clinical Trial Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trial Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Clinical Trial Site
    • Houston, Texas, United States, 77030
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  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Clinical Trial Site
  • Washington
    • Seattle, Washington, United States, 98101
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prednisone group; Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Drug: Prednisone; 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.; Drug: Cyclophosphamide; Orally or intravenously administered; Biological: Rituximab; Intravenously administered; Drug: Azathioprine; Orally administered
Experimental: Avacopan group; Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.	Drug: Cyclophosphamide; Orally or intravenously administered; Biological: Rituximab; Intravenously administered; Drug: Azathioprine; Orally administered; Drug: Avacopan; 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.; Other Names: CCX168

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs	AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse event	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	GTI-CWS=Glucocorticoid Toxicity Index Cumulative Worsening Score; GTI-AIS=Glucocorticoid Toxicity Index Aggregate Improvement Score; The Glucocorticoid Toxicity Index (GTI) was developed to score glucocorticoid toxicity. The GTI includes: the Cumulative Worsening Score (CWS) that captures cumulative toxicity, both permanent and transient, over the course of time (serves as a cumulative record of toxicity); and the Aggregate Improvement Score that captures both improvement and worsening of toxicity over time (serves as a record of both improving and worsening toxicity). Both scores range from 0 (best health) to 100 (worst health).	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	AC=Adjudication Committee; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	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	SF-36v2: Measure of health- related quality of life (Medical Outcomes Survey Short Form-36 version 2) EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels The SF-36v2 component scores and the EQ-5D-5L VAS score range from 0 (worst health) to 100 (best health). The EQ-5D-5L Index Score ranges from 0 (worst health) to 1 (best health).	Baseline, Week 26 and 52
Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study	The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period ANCA=anti-neutrophil cytoplasmic autoantibody; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	Week 52
Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period	The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period The Birmingham Vasculitis Activity Score (BVAS) form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	Week 52
In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks	Change from baseline in kidney function, as measured by eGFR (based on the MDRD equation), was measured in subjects with renal disease based on the BVAS renal component. eGFR=estimated glomerular filtration rate BVAS=Birmingham Vasculitis Activity Score MDRD=Modification of Diet in Renal Disease	Baseline, Week 26 and 52
In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks	BVAS=Birmingham Vasculitis Activity Score UACR=Urinary albumin:creatinine ratio	Baseline, Week 4, 26 and 52
In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks	BVAS=Birmingham Vasculitis Activity Score MCP-1=monocyte chemoattractant protein-1	Baseline, Week 26 and 52
Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points	VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).	Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2)		Baseline, Week 26 and 52
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2)		Baseline, Week 26 and 52
Change From Baseline in Vital Signs (1/5)		Baseline, Week 26 and 52
Change From Baseline in Vital Signs (2/5)		Baseline, Week 26 and 52
Change From Baseline in Vital Signs (3/5)		Baseline, Week 26 and 52
Change From Baseline in Vital Signs (4/5)		Baseline, Week 26 and 52
Change From Baseline in Vital Signs (5/5)	BMI=Body Mass Index	Baseline, Week 26 and 52
Number of Subjects With Clinically Significant ECG Changes From Baseline	Clinical significance was assessed by the individual reading of the ECGs ECG=Electrocardiogram	From day 1 throughout the study period (day 421/week 60)
Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator	AE=Adverse Event	From day 1 throughout the study period (day 421/week 60)
Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity	WBC=White Blood Cell TEAE=Treatment-Emergent Adverse Event	From day 1 throughout the study period (day 421/week 60)
Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study	BVAS=Birmingham Vasculitis Activity Score; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	From day 1 throughout the study period (day 421/week 60)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Soulsby 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.
• Merkel 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.
• Harigai M, Kaname S, Tamura N, Dobashi H, Kubono S, Yoshida T. Efficacy and safety of avacopan in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: A subanalysis of a randomized Phase 3 study. Mod Rheumatol. 2023 Mar 2;33(2):338-345. doi: 10.1093/mr/roac037. Erratum In: Mod Rheumatol. 2024 May 27:roae045. doi: 10.1093/mr/roae045.
• Jayne 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. Erratum In: N Engl J Med. 2024 Jan 25;390(4):388. doi: 10.1056/NEJMx230010.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): September 7, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: December 11, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimated): December 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: complement; ANCA-associated vasculitis; CCX168; vasculitis; C5aR; avacopan; MPA; GPA
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Rituximab; Prednisone; Cyclophosphamide; Azathioprine
• Other Study ID Numbers: CL010_168; ADVOCATE (Other Identifier: ChemoCentryx)

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 (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.
• 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, 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.
• 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