Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
The purpose of this study is to investigate the safety and tolerability of two dose regimens
 of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with
 placebo.
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related
 systemic v anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a
 potentially life-threatening disease.

 GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (e.g.,
 capillaries, venules, arterioles, arteries, and veins). MPA is a necrotizing vasculitis that
 primarily affects capillaries, venules, or arterioles, most commonly manifesting as
 necrotizing glomerulonephritis and/or pulmonary capillaritis. MPA.

 Primed neutrophils are activated by ANCA and generate C5a that engages C5a receptors on
 neutrophils. Therefore, patients with ANCA-related disease have elevated plasma and urine
 levels of C5a in active disease and not in remission.

 IFX-1 is a monoclonal antibody specifically binding to the soluble human complement split
 product C5a and the resulting nearly complete blockade of C5a-induced biological effects may
 be effective in the treatment of subjects with AAV.
Inclusion Criteria:

 1. Male or female, ≥18 years of age.

 2. Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus
 Conference.

 3. Have at least one "major" item, or at least three other items, or at least two renal
 items on the Birmingham Vasculitis Activity Score (BVAS) Version 3.0.

 4. New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs.

 Exclusion Criteria:

 1. Any other multisystem autoimmune disease

 2. Requires mechanical ventilation because of alveolar hemorrhage at Screening.

 3. Human immunodeficiency virus, hepatitis B, or hepatitis C viral screening test showing
 evidence of active or chronic viral infection at Screening or a documented history of
 the human immunodeficiency virus, hepatitis B, or hepatitis C.

 4. Received CYC or RTX 12 weeks before Screening; if on azathioprine (AZA), methotrexate
 (MTX), mycophenolate mofetil (MMF), or mycophenolate sodium (MPS) at the time of
 Screening, these drugs must be withdrawn prior to receiving CYC or RTX.

 5. Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before
 Screening.

 6. On an oral dose of a GC of more than 10 mg prednisone equivalent at Screening or for
 more than 6 weeks before Screening.

 7. Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept,
 alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin
 or plasma exchange, antithymocyte globulin, or required dialysis within 12 weeks
 before Screening.

 8. Received a live vaccination within 4 weeks before Screening or planned between
 Screening and Week 24.

 9. Female subjects of childbearing potential unwilling or unable to use a highly
 effective method of contraception (pearl index <1%) such as complete sexual
 abstinence, combined oral contraceptive, vaginal hormone ring, transdermal
 contraceptive patch, contraceptive implant, or depot contraceptive injection in
 combination with a second method of contraception such as condom, cervical cap, or
 diaphragm with spermicide during the study and for at least 4 weeks after last
 administration of IFX-1 (timeframes for SOC have to be considered as described in the
 respective Prescribing Information).