A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
Condition: ANCA-Associated Vasculitis
MeSH terms: Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Intervention: Avacopan; Prednisone; Cyclophosphamide; Rituximab; Azathioprine
Intervention description: Avacopan 30 mg twice daily orally for 52 weeks (364 days):
- Three 10 mg avacopan capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose.
Oral prednisone-matching placebo tapering regimen over 20 weeks (140 days):
Prednisone-matching placebo capsules equivalent to 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was <55 kg, starting on Day 1 with tapering according to a protocol-specified schedule.
Adolescents who weighed ≤37 kg started at a prednisone-matching placebo dose of 30 mg per day.; Avacopan-matching placebo twice daily orally for 52 weeks (364 days):
- Three avacopan-matching placebo capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose.
Oral prednisone tapering regimen over 20 weeks (140 days):
Prednisone 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was <55 kg, starting on Day 1 with tapering according to the protocol-specified schedule.
Adolescents who weighed ≤37 kg started at a prednisone dose of 30 mg per day.; Orally or intravenously administered; Intravenously administered; Orally administered
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Azathioprine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This study was double-blind, double-dummy, i.e., placebo capsules were identical in appearance to the avacopan capsules, and prednisone capsules also had matching placebo capsules. To maintain the blind, multiple measures were taken (i.e., randomization code was not accessible to study personnel who had contact with study centers or who were involved in data management and analysis for the duration of the study).
Enrollment: 331.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: ANCA-associated vasculitis; complement; vasculitis; C5aR; avacopan; CCX168; MPA; GPA

Summary:

      The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain
      remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or
      in combination with rituximab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic
             polyangiitis

          -  Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed
             associated vasculitis (AAV) where treatment with cyclophosphamide or rituximab is
             needed; where approved by Regulatory Agencies, adolescents (12-17 year old) may be
             enrolled

          -  Use of adequate contraception

          -  Positive test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO)

          -  At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of
             proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS)

          -  Estimated glomerular filtration rate ≥15 mL/minute/1.73 m^2 at screening

        Exclusion Criteria:

          -  Pregnant or breast-feeding

          -  Alveolar hemorrhage requiring pulmonary ventilation support at screening

          -  Any other known multi-system autoimmune disease

          -  Required dialysis or plasma exchange within 12 weeks prior to screening

          -  Have a kidney transplant

          -  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 glucocorticoids, >3000 mg methylprednisolone equivalent, within 4
             weeks prior to screening

          -  Have been taking an oral daily dose of a glucocorticoid of more than 10 mg
             prednisone-equivalent for more than 6 weeks continuously prior to screening

          -  Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks
             provided B cell reconstitution has occurred (i.e., CD19 count > 0.01x10^9/L); received
             anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous
             immunoglobulin (IVIg), belimumab, tocilizumab, or eculizumab within 12 weeks prior to
             screening

          -  For patients scheduled to receive cyclophosphamide treatment, urinary outflow
             obstruction, active infection (especially varicella zoster infection), or platelet
             count <50,000/μL before start of dosing

          -  Participated previously in a CCX168 study