- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01363388
A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background of Cyclophosphamide or Rituximab Treatment
Study Overview
Detailed Description
The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with AAV on background cyclophosphamide or rituximab treatment.
The primary efficacy objective is to evaluate the efficacy of CCX168 based on the Birmingham Vasculitis Activity Score (BVAS) version 3.
The secondary objectives of this study include assessment of the feasibility of reducing or eliminating the use of corticosteroids in the treatment of subjects with ANCA-associated vasculitis without the need for rescue corticosteroid measures and the effect of CCX168 on several disease parameters.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Feldkirch, Austria
-
Innsbruck, Austria
-
Linz, Austria
-
-
-
-
-
Brussels, Belgium
-
Edegem, Belgium
-
Gent, Belgium
-
Leuven, Belgium
-
Liege, Belgium
-
Roeselare, Belgium
-
-
-
-
-
Prague, Czechia
-
-
-
-
-
Bordeaux, France
-
Boulogne sur Mer, France
-
Brest, France
-
Colmar, France
-
Grenoble, France
-
Nantes, France
-
Paris, France
-
Saint Jacques, France
-
Valenciennes, France
-
-
-
-
-
Berlin, Germany
-
Cologne, Germany
-
Dresden, Germany
-
Freiburg, Germany
-
Fulda, Germany
-
Heidelberg, Germany
-
-
-
-
-
Budapest, Hungary
-
-
-
-
-
Groningen, Netherlands
-
Leiden, Netherlands
-
Rotterdam, Netherlands
-
Utrecht, Netherlands
-
-
-
-
-
Bialystok, Poland
-
Katowice, Poland
-
Szczecin, Poland
-
Wroclaw, Poland
-
-
-
-
-
Linkoping, Sweden
-
Lund, Sweden
-
Malmo, Sweden
-
Stockholm, Sweden
-
-
-
-
-
Birmingham, United Kingdom
-
Cambridge, United Kingdom
-
London, United Kingdom
-
Manchester, United Kingdom
-
Oxford, United Kingdom
-
Reading, United Kingdom
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
- Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis or renal limited vasculitis
- Male and postmenopausal or surgically sterile female subjects aged at least 18 years with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be 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
- Estimated glomerular filtration rate (eGFR) ≥ 20mL/min
- Have at least one "major" item, or at least 3 non-major items, or at least 2 renal items on the BVAS version 3
Key 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 of 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 high-dose intravenous corticosteroids within 4 weeks of screening
- On an oral dose of a corticosteroid of more than 10mg prednisone-equivalent at the time of screening
- Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-TNF treatment, abatacept, alemtuzumab, IVIg or plasma exchange within 12 weeks of screening
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Placebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study
|
BID for 84 days
|
Experimental: CCX168
30 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study
|
BID for 84 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Subjects Achieving Disease Response at Day 85
Time Frame: Baseline to Day 85
|
Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.
|
Baseline to Day 85
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients Achieving Renal Response at Day 85
Time Frame: Baseline to Day 85
|
Renal response, assessed in patients with hematuria and albuminuria at baseline, and defined as an improvement in renal parameters, i.e., an increase from baseline to Day 85 in eGFR (Estimated glomerular filtration rate), MDRD (Modification of Diet in Renal Disease), serum creatinine equation, a decrease from baseline to Day 85 in haematuria (central laboratory microscopic count of urinary red blood cells) , decrease from baseline to Day 85 in albuminuria count (first morning UACR (urinary albumin:creatinine ratio).
|
Baseline to Day 85
|
Proportion of Subjects Achieving Disease Remission at Day 85
Time Frame: Day 85
|
Disease remission is defined as BVAS (Birmingham Vasculitis Activity Score) of 0 or 1 plus no worsening in eGFR (Estimated glomerular filtration rate) and urinary RBC (Red Blood cell) count <10/high power field (hpf)
|
Day 85
|
Percent Change From Baseline to Day 85 in BVAS
Time Frame: Baseline to Day 85
|
Percent change in Burmingham Vasculitis Index Score (BVAS) at week 12, higher percentage change indicates worse outcome BVAS = Birmingham Vasculitis Activity Score The 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
|
Change From Baseline to Day 85 in eGFR
Time Frame: Baseline to Day 85
|
eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine
|
Baseline to Day 85
|
Percent Change From Baseline to Day 85 in eGFR
Time Frame: Baseline to Day 85
|
eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine
|
Baseline to Day 85
|
Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period
Time Frame: Baseline to Day 85
|
In subjects with baseline hematuria >5 RBCs/hpf (Red Blood Cell/High Power Field)
|
Baseline to Day 85
|
Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period
Time Frame: Baseline to Day 85
|
In subjects with baseline hematuria <=5 RBCs/hpf (Red Blood Cell/High Power Field)
|
Baseline to Day 85
|
Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period
Time Frame: Baseline to Day 85
|
In subjects with baseline hematuria >=30 RBCs/hpf,(Red Blood Cell/High Power Field)
|
Baseline to Day 85
|
Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period
Time Frame: Baseline to Day 85
|
In subjects with baseline hematuria <=30 RBCs/hpf (Red Blood Cell/High Power Field)
|
Baseline to Day 85
|
Percent Change From Baseline to Day 85 in Urinary RBC Count
Time Frame: Baseline to day 85
|
In subjects with hematuria at baseline, RBC (Red Blood Cell)
|
Baseline to day 85
|
Percent Change From Baseline to Day 85 in UACR
Time Frame: Baseline to Day 85
|
In subjects with albuminuria at baseline UACR (urinary albumin:creatinine ratio)
|
Baseline to Day 85
|
Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio
Time Frame: Baseline to Day 85
|
Urinary Monocyte Chemoattractant Protein-1 (MCP-1):creatinine ratio
|
Baseline to Day 85
|
Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment
Time Frame: Baseline to Day 85
|
Baseline to Day 85
|
|
Change From Baseline to Day 85 in the Vasculitis Damage Index
Time Frame: Baseline to Day 85
|
VDI=Vasculitis Damage Index; The 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-36 v2
Time Frame: Baseline, Day 29 & Day 85
|
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, Day 29 & Day 85
|
Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L
Time Frame: Baseline, Day 29 and Day 85
|
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, Day 29 and Day 85
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Pirow Bekker, MD, PhD, Clinical Trials Disclosure, ChemoCentryx Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CL002_168
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.
Clinical Trials on Vasculitis
-
University Hospital, Strasbourg, FranceRecruiting
-
Xiangya Hospital of Central South UniversityThe Third Xiangya Hospital of Central South University; Hunan Provincial People... and other collaboratorsRecruiting
-
National Institute of Allergy and Infectious Diseases...Immune Tolerance Network (ITN)TerminatedANCA-Associated VasculitisUnited Kingdom
-
Chinese SLE Treatment And Research GroupThe First Affiliated Hospital of Anhui Medical University; Shanghai Zhongshan... and other collaboratorsRecruitingANCA Associated Vasculitis | Maintenance TherapyChina
-
University Hospital, BrestNot yet recruitingOccupational Diseases | ANCA Associated Vasculitis | Environmental ExposureFrance
-
University Hospital Birmingham NHS Foundation TrustMerck Sharp & Dohme LLCRecruitingANCA Associated VasculitisUnited Kingdom
-
University Hospital, BrestRecruiting
-
Nantes University HospitalINSERM UMRS-1064CompletedANCA-associated VasculitisFrance
-
Shanghai Zhongshan HospitalCompletedDrug Use | ANCA Associated Vasculitis | JAK-STAT Pathway DeregulationChina
-
Second Affiliated Hospital, School of Medicine,...RecruitingANCA Associated VasculitisChina
Clinical Trials on CCX168
-
ChemoCentryxCompletedHidradenitis Suppurativa | Acne InversaUnited States
-
Mario Negri Institute for Pharmacological ResearchChemoCentryxTerminated
-
ChemoCentryxCompletedImmunoglobulin A NephropathyUnited States, Sweden
-
AmgenCompletedAnti-neutrophil Cytoplasmic Antibody-associated VasculitisUnited States
-
AmgenCompletedAnti-neutrophil Cytoplasmic Antibody-associated VasculitisUnited States
-
ChemoCentryxMedpace, Inc.CompletedC3 Glomerulopathy (C3G)United States, Spain, France, Netherlands, Belgium, Canada, Denmark, Germany, Ireland, Italy, United Kingdom
-
AmgenCompletedA Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy ParticipantsVasculitis | Systemic Lupus Erythematosus (SLE)Switzerland
-
AmgenCompletedAnti-neutrophil Cytoplasmic Antibody-associated VasculitisJapan
-
AmgenCompletedHepatic ImpairmentUnited States
-
AmgenRecruitingAntineutrophil Cytoplasmic Antibody-associated VasculitisUnited States