Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA
- Conditions
- Granulomatosis With Polyangiitis (GPA)Microscopic Polyangiitis (MPA)
- Interventions
- 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
- 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.
- 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)
Texas Health Resources
🇺🇸Dallas, Texas, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
University of Miami
🇺🇸Miami, Florida, United States
Johns Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
LSU Health Sciences Center Shreveport
🇺🇸Shreveport, Louisiana, United States
Ohio State University Clinical Trials Management Office
🇺🇸Columbus, Ohio, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Altoona Center for Clinical Research, P.C.
🇺🇸Duncansville, Pennsylvania, United States
BRCR Medical Center, Inc.
🇺🇸Camp Hill, Pennsylvania, United States
CHUM Centre de Recherche
🇨🇦Québec, Quebec, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Centre de Recherche Musculo-Squelettique
🇨🇦Trois-Rivières, Quebec, Canada
Low Country Rheumatology, PA
🇺🇸North Charleston, South Carolina, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Texas Research Institute
🇺🇸Fort Worth, Texas, United States
UVA University Physicians Charlottesville
🇺🇸Charlottesville, Virginia, United States
St. Josephs Healthcare
🇨🇦Hamilton, Ontaria, Canada
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Kansas City, Kansas, United States
Science Connections, LLC
🇺🇸Doral, Florida, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Northwell Health, LLC PRIME
🇺🇸New Hyde Park, New York, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Trinity Medical Group
🇺🇸Minot, North Dakota, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Loma Linda University Clinical Trial Center
🇺🇸Loma Linda, California, United States
University of Rochester Medical Center - Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Adriana Pop Moody Clinic PA
🇺🇸Corpus Christi, Texas, United States
University Of MI Medcl Ctr-RHU
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
UNC Kidney Center, UNC-CH Division of Nephrology and Hypertension
🇺🇸Chapel Hill, North Carolina, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States