Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis

July 24, 2023 updated by: ChemoCentryx

A Randomized, Double-Blind, Placebo-Controlled, Dose Assessment Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Funding Source - FDA OOPD

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Complement 5a and its receptor C5aR (CD88) is involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety and efficacy of the C5aR inhibitor CCX168 in subjects with ANCA-associated vasculitis. The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Greenfield Park, Quebec, Canada
      • Levis, Quebec, Canada
  • United States
    • Alabama
      • Huntsville, Alabama, United States
    • Arizona
      • Phoenix, Arizona, United States
      • Tucson, Arizona, United States
    • California
      • Long Beach, California, United States
      • Los Angeles, California, United States
      • San Francisco, California, United States
    • Colorado
      • Aurora, Colorado, United States
    • District of Columbia
      • Washington, District of Columbia, United States
    • Florida
      • Miami Springs, Florida, United States
      • Tampa, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Kentucky
      • Lexington, Kentucky, United States
      • Louisville, Kentucky, United States
    • Louisiana
      • Shreveport, Louisiana, United States
    • Massachusetts
      • Charlestown, Massachusetts, United States
    • Minnesota
      • Duluth, Minnesota, United States
    • Mississippi
      • Tupelo, Mississippi, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • Nevada
      • Reno, Nevada, United States
    • New Hampshire
      • Lebanon, New Hampshire, United States
    • New Mexico
      • Albuquerque, New Mexico, United States
    • New York
      • Great Neck, New York, United States
      • Mineola, New York, United States
      • New York, New York, United States
      • Syracuse, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
      • New Bern, North Carolina, United States
    • Ohio
      • Columbus, Ohio, United States
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
      • Philadelphia, Pennsylvania, United States
    • Rhode Island
      • Providence, Rhode Island, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Tennessee
      • Chattanooga, Tennessee, United States
    • Texas
      • Amarillo, Texas, United States
      • Austin, Texas, United States
      • Houston, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Washington
      • Seattle, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis or renal limited vasculitis
  • Male and female subjects, aged at least 18 years, with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be required
  • Use of adequate contraception during, and for at least the three months after, any administration of study medication is required
  • Positive indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening
  • Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the Birmingham Vasculitis Activity Score (BVAS) version 3
  • Estimated glomerular filtration rate (eGFR) ≥ 20 mL per minute

Exclusion Criteria:

  • Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system involvement
  • Any other multi-system autoimmune disease
  • Medical history of coagulopathy or bleeding disorder
  • 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 corticosteroids, >3000 mg methylprednisolone equivalent, within 12 weeks prior to screening
  • Received an oral daily dose of a corticosteroid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to the screening visit
  • Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or plasma exchange within 12 weeks prior to screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CCX168 low dose plus standard of care
Capsule, 10 mg, twice daily + standard of care for 12 weeks
Drug: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Active Comparator: CCX168 high dose plus standard of care
Capsule, 30 mg, twice daily + standard of care for 12 weeks
Drug: CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids
Placebo Comparator: Placebo, twice daily + standard of care
Capsule, placebo, twice daily + standard of care for 12 weeks
Other: Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: Baseline to Day 85
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Baseline to Day 85
Proportion of Patients Achieving Disease Response Based on BVAS at Day 85
Time Frame: Day 85
Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score [BVAS] at Day 85 and no worsening in any body system component at day 85
Day 85

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
Time Frame: Day 85
Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85.
Day 85
Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.
Time Frame: Day 29 and 85
Proportion of subjects achieving early disease remission based on Birmingham Vasculitis Activity Score (BVAS) score of 0 at Days 29 and 85.
Day 29 and 85
Percent Change From Baseline to Day 85 in BVAS.
Time Frame: Baseline to Day 85
The Birmingham Vasculitis Activity (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). A negative percentage change indicated improvement in health.
Baseline to Day 85
Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85
Time Frame: Day 85
Renal responses among patients (who had hematuria or albuminuria at baseline determined secondary to ANCA-associated vasculitis) were defined as improvement in the following parameters of renal vasculitis: (1) increase from baseline to day 85 in eGFR [Modification of Diet in Renal Disease (MDRD equation)], (2) decrease from baseline to day 85 in hematuria (microscopic count of urinary red blood cells [RBC]), and (3) decrease from baseline to day 85 in albuminuria (first morning urinary albumin:creatinine ratio).
Day 85
Change in Estimated Glomerular Filtration Rate at Day 85
Time Frame: Baseline to Day 85
Mean Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula, for patients with renal disease at baseline.
Baseline to Day 85
Percentage Change in Estimated Glomerular Filtration Rate at Day 85
Time Frame: Baseline to Day 85
Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula.
Baseline to Day 85
Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
Time Frame: Baseline to Day 85
Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline.
Baseline to Day 85
Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85
Time Frame: Baseline to Day 85
Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline
Baseline to Day 85
Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85
Time Frame: Baseline to Day 85
Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline
Baseline to Day 85
Change From Baseline to Day 85 in the VDI
Time Frame: Baseline to Day 85
The Vasculitis Damage Index (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 to Day 85
Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2
Time Frame: Baseline to Day 85
Change from Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the Short Form-36 (SF-36v2) SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health).
Baseline to Day 85
Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L
Time Frame: Baseline to Day 85

Mean Change from baseline to Day 85 in health-related quality-of-life as measured by the Euro Quality-of-Life-5 Domains-5 Levels (EQ-5D-5L).

EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given can be converted into an Index Score ranging from 0 for death to 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst imaginable health) to 100 (the best imaginable health).
Baseline to Day 85
Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85
Time Frame: Baseline to Day 85
Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85
Baseline to Day 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ChemoCentryx

Investigators

  • Principal Investigator: Patrick Nachman, MD, University of North Carolina Kidney Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2015

Primary Completion (Actual)

April 24, 2016

Study Completion (Actual)

July 19, 2016

Study Registration Dates

First Submitted

August 19, 2014

First Submitted That Met QC Criteria

August 20, 2014

First Posted (Estimated)

August 21, 2014

Study Record Updates

Last Update Posted (Actual)

August 16, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL003_168
  • #FD-R-5414 (Other Identifier: Orphan Products Development Grant)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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