study of ifx-1 to replace steroids in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

Conditions: Granulomatosis With Polyangiitis (GPA); Microscopic Polyangiitis (MPA)

Summary: the purpose of the study is to evaluate the efficacy of ifx-1 treatment as replacement for glucocorticoid (gc) therapy in subjects with polyangiitis (gpa) or microscopic polyangiitis (mpa).

anti-neutrophil cytoplasmic antibody-associated vasculitis (aav) is a group of potentially life-threatening autoimmune diseases. preclinical data demonstrate that primed neutrophils are activated by anti-neutrophil cytoplasmic antibody (anca) and generate c5a that engages c5a receptors on neutrophils. patients with anca-related disease have elevated plasma and urine levels of c5a in active disease but not in remission. ifx-1 is as a monoclonal antibody specifically binding to the soluble human complement split product c5a, which results in nearly complete blockade of c5a induced biological effects. therefore, ifx-1 may be effective in the treatment of subjects with aav. in this phase ii study of 20 to 55 subjects with granulomatosis with gpa and mpa, ifx-1 will be administered in combination with reduced dose glucocorticoids or a placebo glucocorticoid compared with standard dose glucocorticoids.

Eligibility criteria:
inclusion criteria: * diagnosis of granulomatosis with polyangiitis (gpa) or microscopic polyangiitis (mpa) * have ≥ 1 "major" item, or ≥ 3 other items, or ≥ 2 renal items on the birmingham vasculitis activity score version 3 (bvasv3). * newly diagnosed or relapsed gpa or mpa that requires treatment with cyclophosphamide (cyc) or rituximab (rtx) plus gcs. * glomerular filtration rate ≥ 20 ml/min/1.73 m². exclusion criteria: * any other multi-system autoimmune disease. * require mechanical ventilation at screening. * known hypersensitivity to any investigational medicinal product and/or any excipient. * rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. * have required management of infections, as follows (a) chronic infection requiring anti-infective therapy within 3 months before screening. (b) use of intravenous antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 30 days of screening * current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence. * evidence of hep b, c and/ or hiv infection. only subjects with documented negative historical results (within 4 weeks before screening) for hep b,c virus and hiv or a negative test by screening can be included into the study. * abnormal laboratory findings at screening * current or history of malignancy, lymphoproliferative, or myeloproliferative disorder * received cyc or rtx within 12 weeks before screening or within 12 weeks before cyc or rtx is started for remission induction within 2 weeks before screening. * received \> 3 g cumulative intravenous gcs within 4 weeks before screening. * received an oral daily dose of a gc of \> 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening. * received an oral daily dose of a gc of \> 80 mg prednisone equivalent within 2 weeks before screening. * received a cd20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin (ig) or plasma exchange, antithymocyte globulin, or required renal dialysis within 12 weeks before screening. * received a live vaccination within 4 weeks before screening * either active or latent tuberculosis treatment is ongoing. * pregnant or lactating. * abnormal electrocardiogram. * female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception * participation in an investigational clinical study during the 12 weeks before screening. * male subjects with female partners of childbearing potential unwilling to use contraception

Keywords: granulomatosis polyangiitis corticosteroid replacement glucocorticoid