A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis

• ClinicalTrials.gov Identifier: NCT01363388
• Recruitment Status: Completed
• First Posted: June 1, 2011
• Results First Posted: July 27, 2020
• Last Update Posted: July 27, 2020
• Sponsor: ChemoCentryx
• Information provided by (Responsible Party): ChemoCentryx

Tracking Information

• First Submitted Date: May 26, 2011
• First Posted Date: June 1, 2011
• Results First Submitted Date: July 7, 2020
• Results First Posted Date: July 27, 2020
• Last Update Posted Date: July 27, 2020
• Study Start Date: August 2011
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 10, 2020): Proportion of Subjects Achieving at Least 50% Reduction in Birmingham Vasculitis Activity Score [BVAS] by Week 12 and No Worsening in Any Body System [ Time Frame: 84 days ]

Original Primary Outcome Measures (submitted: May 30, 2011)

Safety of CCX168 in subjects with AARV [ Time Frame: 169 days ]

Safety assessments include adverse events, physical examination abnormalities, vital signs and clinical laboratory tests (including blood chemistry, hematology and urinalysis).

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: May 30, 2011)

Systemic corticosteroid use [ Time Frame: 169 days ]

Systemic corticosteroid use based on total oral corticosteroid dose and duration of oral corticosteroid use

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis
• Official Title: A 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
• Brief Summary: The aim of this trial is to optimize the treatment to induce remission for patients with non-life-threatening anti-neutrophil cytoplasmic antibody vasculitis (AAV). The intent is to reduce the toxicity of induction therapy by reducing the overall exposure to or eliminating entirely the use of systemic corticosteroids during the induction period with an inhibitor of the complement C5a receptor plus cyclophosphamide or rituximab.

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Vasculitis

Intervention

• Drug: Placebo
  BID for 84 days
• Drug: CCX168
  BID for 84 days

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: CCX168
  Active study medication
  Intervention: Drug: CCX168

• Publications *: Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS. Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. Am J Transplant. 2013 Oct;13(10):2530-9. doi: 10.1111/ajt.12405. Epub 2013 Sep 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 20, 2016): 67
• Original Estimated Enrollment (submitted: May 30, 2011): 60
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Czechia, France, Germany, Hungary, Netherlands, Poland, Sweden, United Kingdom
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01363388
• Other Study ID Numbers: CL002_168
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: ChemoCentryx
• Original Responsible Party: Senior VP Medical and Clinical Affairs, ChemoCentryx Inc
• Current Study Sponsor: ChemoCentryx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pirow Bekker, MD, PhD; ChemoCentryx Inc

• PRS Account: ChemoCentryx
• Verification Date: July 2020