Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis
Condition: ANCA-associated Vasculitis
MeSH terms: Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Intervention: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids; CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids; Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Intervention MeSH terms: Cyclophosphamide; Rituximab; Glucocorticoids
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ANCA-associated vasculitis; complement; vasculitis; C5aR

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
    

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