Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA

InflaRx

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Placebo; Drug: IFX-1 low dose; Drug: IFX-1 high dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT03712345

IFX-1-P2.6

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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20 participants in 3 patient groups, including a placebo group

IFX-1 low dose

Experimental group

Description:

Will receive IFX-1 low dose regimen diluted in sodium chloride solution

Treatment:

Drug: IFX-1 low dose

IFX-1 high dose

Experimental group

Description:

Will receive IFX-1 high dose regimen diluted in sodium chloride solution

Treatment:

Drug: IFX-1 high dose

Placebo

Placebo Comparator group

Description:

Will receive placebo

Treatment:

Drug: Placebo