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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 : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
ChemoCentryx

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).

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

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 : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
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
Study Start Date : December 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vasculitis

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Remission [ Time Frame: 26 weeks ]
    The proportion of patients achieving disease remission assessed by Birmingham Vasculitis Activity Score (BVAS) at Week 26

  2. Sustained remission [ Time Frame: 52 weeks ]
    The proportion of patients achieving sustained disease remission assessed by BVAS at Week 52


Secondary Outcome Measures :
  1. 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

  2. Glucocorticoid-induced toxicity [ Time Frame: 26 weeks ]
    Glucocorticoid-induced toxicity as measured by the Glucocorticoid Toxicity Index

  3. Response rapidity [ Time Frame: 4 weeks ]
    Remission assessed by BVAS at week 4

  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

  5. Estimated glomerular filtration rate (eGFR) [ Time Frame: 52 weeks ]
    Change from baseline in eGFR in mL/min/1.73^2

  6. Urinary albumin:creatinine ratio (UACR) [ Time Frame: 52 weeks ]
    Change from baseline in UACR in mg/g creatinine

  7. 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

  8. Vasculitis Damage Index [ Time Frame: 52 weeks ]
    Change from baseline in the Vasculitis Damage Index (VDI)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

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


  Show 193 Study Locations
Sponsors and Collaborators
ChemoCentryx
Investigators
Study Director: Jan Hillson, MD ChemoCentryx, Inc.

Additional Information:
Responsible Party: ChemoCentryx
ClinicalTrials.gov Identifier: NCT02994927     History of Changes
Other Study ID Numbers: CL010_168
ADVOCATE ( Other Identifier: ChemoCentryx )
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018
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