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

Microscopic Polyangiitis (MPA) Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03712345
• Other study ID #: IFX-1-P2.6
• Status: Terminated
• Phase: Phase 2
• Start date: October 15, 2018
• Est. completion date: May 3, 2021

Study information

• Verified date: May 2022
• Source: InflaRx GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: May 3, 2021
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Granulomatosis with Polyangiitis
• Granulomatosis With Polyangiitis (GPA)
• Microscopic Polyangiitis
• Microscopic Polyangiitis (MPA)
• Systemic Vasculitis

Intervention

Drug:
• IFX-1 low dose
Single IV infusions of IFX-1
• IFX-1 high dose
Single IV infusions of IFX-1
• Placebo
Placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
InflaRx GmbH	Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Percentage of Participants With Clinical Remission (BVAS = 0)	Efficacy Endpoint that evaluates participants with complete remission	Week 16
Secondary	IFX-1 Concentration Pre-dose	Assess the pharmacokinetic of the investigational medicinal product.	Week 16
Secondary	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
Secondary	C5a Plasma Concentration	Pharmacodynamic parameter concentration	Week 16
Secondary	IFX-1 Blocking Activity 2.5 nM	Pharmacodynamic Parameter of IFX-1 blocking activity 2.5 nM	Week 16
Secondary	IFX-1 Blocking Activity 10 nM	Pharmacodynamic Parameter of IFX-1 blocking activity 10 nM	Week 16