Clinical trial NCT03712345: Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Efficacy and Safety Study of IFX-1 in Add-On to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Granulomatosis With Polyangiitis (GPA)
Microscopic Polyangiitis (MPA)
Keywords: Granulomatosis with Polyangiitis (GPA)
Microscopic Polyangiitis (MPA)
IFX-1
ANCA
AAV
Lead sponsor: InflaRx GmbH
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2018-10-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number and Percentage of Participants With at Least One TEAE Per Treatment Group.
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Response
timeFrame: Week 16
measure: Percentage of Participants With Clinical Remission (BVAS = 0)
timeFrame: Week 16
measure: IFX-1 Concentration Pre-dose
timeFrame: Week 16
measure: 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
timeFrame: Weeks 1, 4 and 16
measure: C5a Plasma Concentration
timeFrame: Week 16
measure: IFX-1 Blocking Activity 2.5 nM
timeFrame: Week 16
measure: IFX-1 Blocking Activity 10 nM
timeFrame: Week 16
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Clinical Trial Center
state: California
city: Doral
country: United States
facility: Science Connections, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Shreveport
country: United States
facility: LSU Health Sciences Center Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of MI Medcl Ctr-RHU
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New Hyde Park
country: United States
facility: Northwell Health, LLC PRIME
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - Strong Memorial Hospital
state: New York
city: Chapel Hill
country: United States
facility: UNC Kidney Center, UNC-CH Division of Nephrology and Hypertension
state: North Carolina
city: Minot
country: United States
facility: Trinity Medical Group
state: North Dakota
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Camp Hill
country: United States
facility: BRCR Medical Center, Inc.
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research, P.C.
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: North Charleston
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Corpus Christi
country: United States
facility: Adriana Pop Moody Clinic PA
state: Texas
city: Dallas
country: United States
facility: Texas Health Resources
state: Texas
city: Fort Worth
country: United States
facility: Texas Research Institute
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Charlottesville
country: United States
facility: UVA University Physicians Charlottesville
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: St. Josephs Healthcare
state: Ontaria
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Québec
country: Canada
facility: CHUM Centre de Recherche
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre de Recherche Musculo-Squelettique
state: Quebec
Study officials:
affiliation: InflaRx GmbH
name: Korinna Pilz, MD, MS
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Peter A. Merkel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Serling-Boyd N, Wallace ZS. Management of primary vasculitides with biologic and novel small molecule medications. Curr Opin Rheumatol. 2021 Jan;33(1):8-14. doi: 10.1097/BOR.0000000000000756.