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

Phase 2

Terminated

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

Interventions: Drug: IFX-1 high dose
Drug: Placebo
Drug: IFX-1 low dose

Registration Number: NCT03712345

Lead Sponsor: InflaRx GmbH

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Male or female, ≥18 years of age.
Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference.
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.
New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs.

Exclusion Criteria

Any other multisystem autoimmune disease
Requires mechanical ventilation because of alveolar hemorrhage at Screening.
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.
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.
Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before Screening.
On an oral dose of a GC of more than 10 mg prednisone equivalent at Screening or for more than 6 weeks before Screening.
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.
Received a live vaccination within 4 weeks before Screening or planned between Screening and Week 24.
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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IFX-1 high dose	IFX-1 high dose	Will receive IFX-1 high dose regimen diluted in sodium chloride solution
Placebo	Placebo	Will receive placebo
IFX-1 low dose	IFX-1 low dose	Will receive IFX-1 low dose regimen diluted in sodium chloride solution

Primary Outcome Measures

Name	Time	Method
Number and Percentage of Participants With at Least One TEAE Per Treatment Group.	Week 24	Number and percentage of participants who experience at least one treatment-emergent adverse event (TEAE) per treatment group.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Clinical Response	Week 16	Efficacy Endpoint based on clinical response evaluated through BVAS. Clinical response is defined as a reduction in BVAS of ≥50% and no worsening in any body system and no administration of rescue medication prior to the response assessment.
Percentage of Participants With Clinical Remission (BVAS = 0)	Week 16	Efficacy Endpoint that evaluates participants with complete remission
IFX-1 Concentration Pre-dose	Week 16	Assess the pharmacokinetic of the investigational medicinal product.
IFX 1 Concentration at Predose (0 Hours), After the End of the Infusion (+10minutes), and at 2, 6, 24, and 48 Hours After the Start of the Infusion for Participants in the PK Substudy	Weeks 1, 4 and 16	Analyze the IMP plasma concentration using a PK model: IFX 1 concentration at predose (0 hours), after the end of the infusion (+10minutes), and at 2, 6, 24, and 48 hours after the start of the infusion for participants in the PK substudy
C5a Plasma Concentration	Week 16	Pharmacodynamic parameter concentration
IFX-1 Blocking Activity 2.5 nM	Week 16	Pharmacodynamic Parameter of IFX-1 blocking activity 2.5 nM
IFX-1 Blocking Activity 10 nM	Week 16	Pharmacodynamic Parameter of IFX-1 blocking activity 10 nM

Trial Locations

Locations (38): Mayo Clinic Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Loma Linda University Clinical Trial Center
🇺🇸
Loma Linda, California, United States
Science Connections, LLC
🇺🇸
Doral, Florida, United States
University of Miami
🇺🇸
Miami, Florida, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸
Kansas City, Kansas, United States
LSU Health Sciences Center Shreveport
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Shreveport, Louisiana, United States
Johns Hopkins Bayview Medical Center
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University Of MI Medcl Ctr-RHU
🇺🇸
Ann Arbor, Michigan, United States
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Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States