A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis

Amgen

Status and phase: Completed; Phase 2

Conditions: Vasculitis

Treatments: Drug: CCX168; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01363388

CL002_168

Details and patient eligibility

About

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.

Full 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.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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67 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study

Treatment:

Drug: Placebo

CCX168

Experimental group

Description:

30 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study

Treatment:

Drug: CCX168