Clinical trial NCT02222155: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: ANCA-associated Vasculitis
Keywords: ANCA-associated vasculitis
complement
vasculitis
C5aR
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-08-21
Enrollment: 42
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 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).

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

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

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: Baseline to Day 85
measure: Proportion of Patients Achieving Disease Response Based on BVAS at Day 85
timeFrame: Day 85
Secondary outcomes:
measure: Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
timeFrame: Day 85
measure: Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.
timeFrame: Day 29 and 85
measure: Percent Change From Baseline to Day 85 in BVAS.
timeFrame: Baseline to Day 85
measure: Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85
timeFrame: Day 85
measure: Change in Estimated Glomerular Filtration Rate at Day 85
timeFrame: Baseline to Day 85
measure: Percentage Change in Estimated Glomerular Filtration Rate at Day 85
timeFrame: Baseline to Day 85
measure: Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
timeFrame: Baseline to Day 85
measure: Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85
timeFrame: Baseline to Day 85
measure: Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85
timeFrame: Baseline to Day 85
measure: Change From Baseline to Day 85 in the VDI
timeFrame: Baseline to Day 85
measure: Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2
timeFrame: Baseline to Day 85
measure: Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L
timeFrame: Baseline to Day 85
measure: Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85
timeFrame: Baseline to Day 85
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Miami Springs
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Charlestown
country: United States
state: Massachusetts
city: Duluth
country: United States
state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Reno
country: United States
state: Nevada
city: Lebanon
country: United States
state: New Hampshire
city: Albuquerque
country: United States
state: New Mexico
city: Great Neck
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: New Bern
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Levis
country: Canada
state: Quebec
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.