Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis

Amgen42 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

ANCA-associated Vasculitis

Interventions

CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoidsDRUG

CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoidsDRUG

Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoidsOTHER

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (43)

Outcomes

Primary Outcomes

Incidence of Adverse Events

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

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

Time frame: Day 85

Secondary Outcomes

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.

Time frame: 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.

Time frame: Day 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.

Time frame: Baseline to Day 85

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).

Data from ClinicalTrials.gov

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Unnamed facility

Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Miami Springs, Florida, United States

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Tampa, Florida, United States

...and 33 more locations