Back to resultsClinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis
Primary Purpose
ANCA-associated Vasculitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids
Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Sponsored by
About this trial
This is an interventional treatment trial for ANCA-associated Vasculitis focused on measuring ANCA-associated vasculitis, complement, vasculitis, C5aR
Eligibility Criteria
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to screening; if on azathioprine, mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
CCX168 low dose plus standard of care
CCX168 high dose plus standard of care
Placebo, twice daily + standard of care
Arm Description
Capsule, 10 mg, twice daily + standard of care for 12 weeks
Capsule, 30 mg, twice daily + standard of care for 12 weeks
Capsule, placebo, twice daily + standard of care for 12 weeks
Outcomes
Primary Outcome Measures
Incidence of Adverse Events
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Proportion of Patients Achieving Disease Response Based on BVAS at 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
Secondary Outcome Measures
Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85.
Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 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.
Percent Change From Baseline to Day 85 in BVAS.
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.
Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at 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).
Change in Estimated Glomerular Filtration Rate at 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.
Percentage Change in Estimated Glomerular Filtration Rate at Day 85
Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula.
Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline.
Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85
Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline
Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85
Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline
Change From Baseline to Day 85 in the VDI
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)
Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2
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).
Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L
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).
Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85
Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02222155
Brief Title
Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
February 4, 2015 (Actual)
Primary Completion Date
April 24, 2016 (Actual)
Study Completion Date
July 19, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ChemoCentryx
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ANCA-associated Vasculitis
Keywords
ANCA-associated vasculitis, complement, vasculitis, C5aR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CCX168 low dose plus standard of care
Arm Type
Active Comparator
Arm Description
Capsule, 10 mg, twice daily + standard of care for 12 weeks
Arm Title
CCX168 high dose plus standard of care
Arm Type
Active Comparator
Arm Description
Capsule, 30 mg, twice daily + standard of care for 12 weeks
Arm Title
Placebo, twice daily + standard of care
Arm Type
Placebo Comparator
Arm Description
Capsule, placebo, twice daily + standard of care for 12 weeks
Intervention Type
Drug
Intervention Name(s)
CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Intervention Type
Drug
Intervention Name(s)
CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids
Intervention Type
Other
Intervention Name(s)
Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Time Frame
Baseline to Day 85
Title
Proportion of Patients Achieving Disease Response Based on BVAS at Day 85
Description
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
Time Frame
Day 85
Secondary Outcome Measure Information:
Title
Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
Description
Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85.
Time Frame
Day 85
Title
Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.
Description
Proportion of subjects achieving early disease remission based on Birmingham Vasculitis Activity Score (BVAS) score of 0 at Days 29 and 85.
Time Frame
Day 29 and 85
Title
Percent Change From Baseline to Day 85 in BVAS.
Description
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.
Time Frame
Baseline to Day 85
Title
Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85
Description
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).
Time Frame
Day 85
Title
Change in Estimated Glomerular Filtration Rate at Day 85
Description
Mean Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula, for patients with renal disease at baseline.
Time Frame
Baseline to Day 85
Title
Percentage Change in Estimated Glomerular Filtration Rate at Day 85
Description
Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula.
Time Frame
Baseline to Day 85
Title
Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
Description
Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline.
Time Frame
Baseline to Day 85
Title
Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85
Description
Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline
Time Frame
Baseline to Day 85
Title
Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85
Description
Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline
Time Frame
Baseline to Day 85
Title
Change From Baseline to Day 85 in the VDI
Description
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)
Time Frame
Baseline to Day 85
Title
Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2
Description
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).
Time Frame
Baseline to Day 85
Title
Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L
Description
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).
Time Frame
Baseline to Day 85
Title
Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85
Description
Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85
Time Frame
Baseline to Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Nachman, MD
Organizational Affiliation
University of North Carolina Kidney Center
Official's Role
Principal Investigator
Facility Information:
City
Huntsville
State/Province
Alabama
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United States
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Phoenix
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Arizona
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United States
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Tucson
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Arizona
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Long Beach
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California
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Los Angeles
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San Francisco
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California
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Aurora
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Colorado
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Washington
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District of Columbia
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Miami Springs
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Tampa
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Chicago
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Illinois
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Kansas City
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Kansas
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Lexington
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Kentucky
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Louisville
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Kentucky
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Shreveport
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Louisiana
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Charlestown
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Massachusetts
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Duluth
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Minnesota
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Tupelo
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Mississippi
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Saint Louis
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Missouri
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Reno
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Nevada
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Lebanon
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New Hampshire
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Albuquerque
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New Mexico
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Great Neck
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New York
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United States
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Mineola
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New York
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United States
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New York
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New York
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Syracuse
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New York
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United States
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Chapel Hill
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North Carolina
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United States
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New Bern
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North Carolina
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Columbus
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Ohio
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Duncansville
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Pennsylvania
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Philadelphia
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Pennsylvania
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Providence
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Rhode Island
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Charleston
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South Carolina
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Chattanooga
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Tennessee
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United States
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Amarillo
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Texas
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United States
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Austin
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Texas
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United States
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Houston
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Texas
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Salt Lake City
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Utah
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United States
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Seattle
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Washington
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United States
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Calgary
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Alberta
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Canada
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Toronto
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Ontario
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Canada
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Greenfield Park
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Quebec
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Canada
City
Levis
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
33128347
Citation
Merkel PA, Niles J, Jimenez R, Spiera RF, Rovin BH, Bomback A, Pagnoux C, Potarca A, Schall TJ, Bekker P; CLASSIC Investigators. Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. ACR Open Rheumatol. 2020 Nov;2(11):662-671. doi: 10.1002/acr2.11185. Epub 2020 Oct 31.
Results Reference
derived
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Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis
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