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

This study is currently recruiting participants.
Verified November 2017 by ChemoCentryx
Sponsor:
ClinicalTrials.gov Identifier:
NCT02994927
First Posted: December 16, 2016
Last Update Posted: November 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
ChemoCentryx
  Purpose
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).

Condition Intervention Phase
ANCA-Associated Vasculitis Drug: CCX168 Drug: Prednisone Drug: Cyclophosphamide Biological: Rituximab Drug: Azathioprine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by ChemoCentryx:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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)


Estimated Enrollment: 300
Study Start Date: December 2016
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CCX168 (avacopan)
CCX168 in combination with rituximab or in combination with cyclophosphamide followed by azathioprine
Drug: CCX168
Orally administered
Other Name: Avacopan
Drug: Cyclophosphamide
Orally or intravenously administered
Biological: Rituximab
Intravenously administered
Drug: Azathioprine
Orally administered
Active Comparator: Prednisone
Prednisone in combination with rituximab or in combination with cyclophosphamide followed by azathioprine
Drug: Prednisone
Orally administered
Drug: Cyclophosphamide
Orally or intravenously administered
Biological: Rituximab
Intravenously administered
Drug: Azathioprine
Orally administered

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02994927


Contacts
Contact: A. Potarca +31.6.3089.2290 apotarca@chemocentryx.com

  Show 164 Study Locations
Sponsors and Collaborators
ChemoCentryx
Investigators
Study Director: Jan Hillson, MD ChemoCentryx, Inc.
  More Information

Additional Information:
Responsible Party: ChemoCentryx
ClinicalTrials.gov Identifier: NCT02994927     History of Changes
Other Study ID Numbers: CL010_168
ADVOCATE ( Other Identifier: ChemoCentryx )
First Submitted: December 11, 2016
First Posted: December 16, 2016
Last Update Posted: November 10, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by ChemoCentryx:
ANCA-associated vasculitis
complement
vasculitis
C5aR
avacopan
CCX168
MPA
GPA

Additional relevant MeSH terms:
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vascular Diseases
Cardiovascular Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Azathioprine
Rituximab
Prednisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antimetabolites
Antimetabolites, Antineoplastic