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A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis (ADVOCATE)

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ClinicalTrials.gov Identifier: NCT02994927
Recruitment Status : Active, not recruiting
First Posted : December 16, 2016
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
ChemoCentryx

Tracking Information
First Submitted Date  ICMJE December 11, 2016
First Posted Date  ICMJE December 16, 2016
Last Update Posted Date July 8, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
  • Remission [ Time Frame: 26 weeks ]
    The proportion of patients achieving disease remission assessed by Birmingham Vasculitis Activity Score (BVAS) at Week 26
  • Sustained remission [ Time Frame: 52 weeks ]
    The proportion of patients achieving sustained disease remission assessed by BVAS at Week 52
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02994927 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
  • Adverse events coded by MedDRA [ Time Frame: 60 weeks ]
    Patient incidence of treatment-emergent serious adverse events, adverse events, and withdrawals due to adverse events
  • Glucocorticoid-induced toxicity [ Time Frame: 26 weeks ]
    Glucocorticoid-induced toxicity as measured by the Glucocorticoid Toxicity Index
  • Response rapidity [ Time Frame: 4 weeks ]
    Remission assessed by BVAS at week 4
  • Health-related quality of life [ Time Frame: 52 weeks ]
    Change in health-related quality-of-life based on the Short Form-36 version 2 component and domain scores and the EuroQOL-5D-5L visual analogue scale (in mm) and index
  • Estimated glomerular filtration rate (eGFR) [ Time Frame: 52 weeks ]
    Change from baseline in eGFR in mL/min/1.73^2
  • Urinary albumin:creatinine ratio (UACR) [ Time Frame: 52 weeks ]
    Change from baseline in UACR in mg/g creatinine
  • Urinary monocyte chemoattractant protein-1 (MCP-1):creatinine ratio [ Time Frame: 52 weeks ]
    Change from baseline in urinary MCP-1:creatinine ratio in pg/mg creatinine
  • Vasculitis Damage Index [ Time Frame: 52 weeks ]
    Change from baseline in the Vasculitis Damage Index (VDI)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
Official Title  ICMJE 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
Brief Summary The aim of the trial is to assess the safety and efficacy of the orally-administered, selective complement C5a receptor inhibitor CCX168 (avacopan) in inducing and sustaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE ANCA-Associated Vasculitis
Intervention  ICMJE
  • Drug: CCX168
    Orally administered
    Other Name: Avacopan
  • Drug: Prednisone
    Orally administered
  • Drug: Cyclophosphamide
    Orally or intravenously administered
  • Biological: Rituximab
    Intravenously administered
  • Drug: Azathioprine
    Orally administered
Study Arms  ICMJE
  • Experimental: CCX168 (avacopan)
    CCX168 in combination with rituximab or in combination with cyclophosphamide followed by azathioprine
    Interventions:
    • Drug: CCX168
    • Drug: Cyclophosphamide
    • Biological: Rituximab
    • Drug: Azathioprine
  • Active Comparator: Prednisone
    Prednisone in combination with rituximab or in combination with cyclophosphamide followed by azathioprine
    Interventions:
    • Drug: Prednisone
    • Drug: Cyclophosphamide
    • Biological: Rituximab
    • Drug: Azathioprine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 13, 2016)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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-PR3 or anti-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 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-TNF treatment, abatacept, alemtuzumab, 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Ireland,   Italy,   Japan,   Netherlands,   New Zealand,   Norway,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02994927
Other Study ID Numbers  ICMJE CL010_168
ADVOCATE ( Other Identifier: ChemoCentryx )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ChemoCentryx
Study Sponsor  ICMJE ChemoCentryx
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Cass Kelleher, MD ChemoCentryx, Inc.
PRS Account ChemoCentryx
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP