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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Granulomatosis With Polyangiitis (GPA); Microscopic Polyangiitis (MPA)
• Intervention / Treatment: Drug: Placebo; Drug: IFX-1 low dose; Drug: IFX-1 high dose

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontaria
    • Hamilton, Ontaria, Canada, L8N 4A6
      • St. Josephs Healthcare
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Québec, Quebec, Canada, H2X 0A9
      • CHUM Centre de Recherche
    • Trois-Rivières, Quebec, Canada, G8Z1Y2
      • Centre De Recherche Musculo-Squelettique
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Clinical Trial Center
  • Florida
    • Doral, Florida, United States, 33166
      • Science Connections, LLC
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc.
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University Of MI Medcl Ctr-RHU
    • Detroit, Michigan, United States, 48084
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health, LLC PRIME
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center - Strong Memorial Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7155
      • UNC Kidney Center, UNC-CH Division of Nephrology and Hypertension
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Medical Group
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Ohio State University Clinical Trials Management Office
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • BRCR Medical Center, Inc.
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research, P.C.
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Adriana Pop Moody Clinic PA
    • Dallas, Texas, United States, 75287
      • Texas Health Resources
    • Fort Worth, Texas, United States, 76104
      • Texas Research Institute
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions, Inc.
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • UVA University Physicians Charlottesville
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IFX-1 low dose; Will receive IFX-1 low dose regimen diluted in sodium chloride solution	Drug: IFX-1 low dose; Single IV infusions of IFX-1; Other Names: CaCP29
EXPERIMENTAL: IFX-1 high dose; Will receive IFX-1 high dose regimen diluted in sodium chloride solution	Drug: IFX-1 high dose; Single IV infusions of IFX-1; Other Names: CaCP29
PLACEBO_COMPARATOR: Placebo; Will receive placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Clinical Response	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.	Week 16
Percentage of Participants With Clinical Remission (BVAS = 0)	Efficacy Endpoint that evaluates participants with complete remission	Week 16
IFX-1 Concentration Pre-dose	Assess the pharmacokinetic of the investigational medicinal product.	Week 16
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	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	Weeks 1, 4 and 16
C5a Plasma Concentration	Pharmacodynamic parameter concentration	Week 16
IFX-1 Blocking Activity 2.5 nM	Pharmacodynamic Parameter of IFX-1 blocking activity 2.5 nM	Week 16
IFX-1 Blocking Activity 10 nM	Pharmacodynamic Parameter of IFX-1 blocking activity 10 nM	Week 16

Collaborators and Investigators

• Sponsor: InflaRx GmbH
• Collaborators: Iqvia Pty Ltd
• Investigators: Study Director: Korinna Pilz, MD, MS, InflaRx GmbH

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2018
• Primary Completion (ACTUAL): September 10, 2020
• Study Completion (ACTUAL): May 3, 2021

Study Registration Dates

• First Submitted: October 16, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (ACTUAL): October 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: AAV; ANCA; IFX-1; Granulomatosis with Polyangiitis (GPA); Microscopic Polyangiitis (MPA)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Lung Diseases; Vasculitis; Lung Diseases, Interstitial; Cerebral Small Vessel Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Systemic Vasculitis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Vilobelimab
• Other Study ID Numbers: IFX-1-P2.6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No