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

Amgen

Status and phase: Completed; Phase 2

Conditions: ANCA-associated Vasculitis

Treatments: Drug: CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids; Other: Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids; Drug: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids

Study type: Interventional

Funder types: Industry

Identifiers

NCT02222155

CL003_168

#FD-R-5414 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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42 participants in 3 patient groups, including a placebo group

CCX168 low dose plus standard of care

Active Comparator group

Description:

Capsule, 10 mg, twice daily + standard of care for 12 weeks

Treatment:

Drug: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids

CCX168 high dose plus standard of care

Active Comparator group

Description:

Capsule, 30 mg, twice daily + standard of care for 12 weeks

Treatment:

Drug: CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids

Placebo, twice daily + standard of care

Placebo Comparator group

Description:

Capsule, placebo, twice daily + standard of care for 12 weeks

Treatment:

Other: Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids