Study of IFX-1 to Replace Steroids in Patients With Granulomatosis With Polyangiitis and Microscopic Polyangiitis.

A Randomized, Double-blind, Double-dummy, Active-controlled, Multicenter, 2-part Phase II Study on Replacement of Steroids by IFX-1 in Active Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)

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.

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