Clinical trial NCT01363388: A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vasculitis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-06-01
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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 acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

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

Primary outcomes:
measure: Proportion of Subjects Achieving Disease Response at Day 85
timeFrame: Baseline to Day 85
Secondary outcomes:
measure: Proportion of Patients Achieving Renal Response at Day 85
timeFrame: Baseline to Day 85
measure: Proportion of Subjects Achieving Disease Remission at Day 85
timeFrame: Day 85
measure: Percent Change From Baseline to Day 85 in BVAS
timeFrame: Baseline to Day 85
measure: Change From Baseline to Day 85 in eGFR
timeFrame: Baseline to Day 85
measure: Percent Change From Baseline to Day 85 in eGFR
timeFrame: Baseline to Day 85
measure: Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period
timeFrame: Baseline to Day 85
measure: Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period
timeFrame: Baseline to Day 85
measure: Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period
timeFrame: Baseline to Day 85
measure: Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period
timeFrame: Baseline to Day 85
measure: Percent Change From Baseline to Day 85 in Urinary RBC Count
timeFrame: Baseline to day 85
measure: Percent Change From Baseline to Day 85 in UACR
timeFrame: Baseline to Day 85
measure: Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio
timeFrame: Baseline to Day 85
measure: Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment
timeFrame: Baseline to Day 85
measure: Change From Baseline to Day 85 in the Vasculitis Damage Index
timeFrame: Baseline to Day 85
measure: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2
timeFrame: Baseline, Day 29 & Day 85
measure: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L
timeFrame: Baseline, Day 29 and Day 85
Other outcomes:
Locations:
city: Feldkirch
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Brussels
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Roeselare
country: Belgium
city: Prague
country: Czechia
city: Bordeaux
country: France
city: Boulogne sur Mer
country: France
city: Brest
country: France
city: Colmar
country: France
city: Grenoble
country: France
city: Nantes
country: France
city: Paris
country: France
city: Saint Jacques
country: France
city: Valenciennes
country: France
city: Berlin
country: Germany
city: Cologne
country: Germany
city: Dresden
country: Germany
city: Freiburg
country: Germany
city: Fulda
country: Germany
city: Heidelberg
country: Germany
city: Budapest
country: Hungary
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Bialystok
country: Poland
city: Katowice
country: Poland
city: Szczecin
country: Poland
city: Wroclaw
country: Poland
city: Linkoping
country: Sweden
city: Lund
country: Sweden
city: Malmo
country: Sweden
city: Stockholm
country: Sweden
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Oxford
country: United Kingdom
city: Reading
country: United Kingdom
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.