Study of IFX-1 to Replace Steroids in Patients With Granulomatosis With Polyangiitis and Microscopic Polyangiitis. (IXchange)

August 3, 2022 updated by: InflaRx GmbH

A Randomized, Double-blind, Double-dummy, Active-controlled, Multicenter, 2-part Phase II Study on Replacement of Steroids by IFX-1 in Active Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)

The purpose of the study is to evaluate the efficacy of IFX-1 treatment as replacement for glucocorticoid (GC) therapy in subjects with polyangiitis (GPA) or microscopic polyangiitis (MPA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. Preclinical data demonstrate that primed neutrophils are activated by anti-neutrophil cytoplasmic antibody (ANCA) and generate C5a that engages C5a receptors on neutrophils. Patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease but not in remission. IFX-1 is as a monoclonal antibody specifically binding to the soluble human complement split product C5a, which results in nearly complete blockade of C5a induced biological effects. Therefore, IFX-1 may be effective in the treatment of subjects with AAV.

In this Phase II study of 20 to 55 subjects with granulomatosis with GPA and MPA, IFX-1 will be administered in combination with reduced dose glucocorticoids or a placebo glucocorticoid compared with standard dose glucocorticoids.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • Clinical Site
      • Liège, Belgium
        • Clinical Site
  • Czechia
      • Hradec Králové, Czechia
        • Clinical Site
      • Prague, Czechia, 150 06
        • Clinical Site
      • Praha, Czechia, 128 08
        • Clinical Site
      • Praha, Czechia, 140 21
        • Clinical Site
  • France
      • Angers, France
        • Clinical Site
      • Brest, France
        • Clinical Site
      • Créteil, France
        • Clinical Site
      • Grenoble, France
        • Clinical Site
      • Lille, France
        • Clinical Site
      • Montpellier, France
        • Clinical Site
      • Paris, France, 75012
        • Clinical Site
      • Paris, France, 75651
        • Clinical Site
      • Paris, France, 75679
        • Clinical Site
      • Pessac, France
        • Clinical Site
      • Poitiers, France
        • Clinical Site
  • Germany
      • Aachen, Germany
        • Clinical Site
      • Berlin, Germany
        • Clinical Site
      • Dresden, Germany
        • Clinical Site
      • Essen, Germany
        • Clinical Site
      • Freiburg, Germany
        • Clinical Site
      • Hannover, Germany
        • Clinical Site
      • Kirchheim unter Teck, Germany
        • Clinical Site
      • Köln, Germany
        • Clinical Site
      • Leipzig, Germany
        • Clinical Site
      • Ludwigshafen, Germany
        • Clinical Site
      • Mannheim, Germany
        • Clinical Site
      • Münster, Germany
        • Clinical Site
      • Stuttgart, Germany
        • Clinical Site
    • Thüringen
      • Jena, Thüringen, Germany
        • Clinical Site
  • Italy
      • Catania, Italy
        • Clinical Site
      • Lecco, Italy
        • Clinical Site
      • Messina, Italy
        • Clinical Site
      • Milano, Italy, 20132
        • Clinical Site
      • Milano, Italy, 20153
        • Clinical Site
      • Monza, Italy
        • Clinical Site
      • Pavia, Italy
        • Clinical Site
      • Pisa, Italy
        • Clinical Site
      • Verona, Italy
        • Clinical Site
  • Netherlands
      • Maastricht, Netherlands
        • Clinical Site
      • Rotterdam, Netherlands
        • Clinical Site
  • Russian Federation
      • Kemerovo, Russian Federation
        • Clinical Site
      • Moscow, Russian Federation, 119991
        • Clinical Site
      • Moscow, Russian Federation, 121374
        • Clinical Site
      • Moscow, Russian Federation, 129110
        • Clinical Site
      • Orenburg, Russian Federation
        • Clinical Site
      • Petrozavodsk, Russian Federation
        • Clinical Site
      • Saratov, Russian Federation, 410039
        • Clinical Site
      • Saratov, Russian Federation, 410053
        • Clinical Site
      • Yaroslavl, Russian Federation
        • Clinical Site
  • Spain
      • Alcorcón, Spain
        • Clinical Site
      • Badalona, Spain
        • Clinical Site
      • Barcelona, Spain
        • Clinical Site
      • Barcelona, Spain, 08025
        • Clinical Site
      • Barcelona, Spain, 08036
        • Clinical Site
      • Fuenlabrada, Spain
        • Clinical Site
      • L'Hospitalet De Llobregat, Spain
        • Clinical Site
      • Sevilla, Spain, 41010
        • Clinical Site
      • Sevilla, Spain, 41013
        • Clinical Site
      • Sevilla, Spain, 41014
        • Clinical Site
  • Sweden
      • Göteborg, Sweden
        • Clinical Site
      • Stockholm, Sweden
        • Clinical Site
      • Uppsala, Sweden
        • Clinical Site
  • Switzerland
      • Saint Gallen, Switzerland
        • Clinical Site
      • Zuerich, Switzerland
        • Clinical Site
  • United Kingdom
      • Aberdeen, United Kingdom
        • Clinical Site
      • Cambridge, United Kingdom
        • Clinical Site
      • Cardiff, United Kingdom
        • Clinical Site
      • Leicester, United Kingdom
        • Clinical Site
      • London, United Kingdom, NW3 2QG
        • Clinical Site
      • London, United Kingdom, SE1 9RT
        • Clinical Site
      • Portsmouth, United Kingdom
        • Clinical Site
      • Preston, United Kingdom
        • Clinical Site
      • Reading, United Kingdom
        • Clinical Site
      • Sheffield, United Kingdom
        • Clinical Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
  • Have ≥ 1 "major" item, or ≥ 3 other items, or ≥ 2 renal items on the Birmingham Vasculitis Activity Score Version 3 (BVASv3).
  • Newly diagnosed or relapsed GPA or MPA that requires treatment with Cyclophosphamide (CYC) or Rituximab (RTX) plus GCs.
  • Glomerular filtration rate ≥ 20 mL/min/1.73 m².

Exclusion Criteria:

  • Any other multi-system autoimmune disease.
  • Require mechanical ventilation at screening.
  • Known hypersensitivity to any investigational medicinal product and/or any excipient.
  • Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
  • Have required management of infections, as follows (a) Chronic infection requiring anti-infective therapy within 3 months before screening. (b) Use of intravenous antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 30 days of screening
  • Current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence.
  • Evidence of Hep B, C and/ or HIV infection. Only subjects with documented negative historical results (within 4 weeks before screening) for Hep B,C Virus and HIV or a negative test by Screening can be included into the study.
  • Abnormal laboratory findings at screening
  • Current or history of malignancy, lymphoproliferative, or myeloproliferative disorder
  • Received CYC or RTX within 12 weeks before screening or within 12 weeks before CYC or RTX is started for remission induction within 2 weeks before screening.
  • Received > 3 g cumulative intravenous GCs within 4 weeks before screening.
  • Received an oral daily dose of a GC of > 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening.
  • Received an oral daily dose of a GC of > 80 mg prednisone equivalent within 2 weeks before screening.
  • Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin (Ig) or plasma exchange, antithymocyte globulin, or required renal dialysis within 12 weeks before screening.
  • Received a live vaccination within 4 weeks before screening
  • Either active or latent tuberculosis treatment is ongoing.
  • Pregnant or lactating.
  • Abnormal electrocardiogram.
  • Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception
  • Participation in an investigational clinical study during the 12 weeks before screening.
  • Male subjects with female partners of childbearing potential unwilling to use contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A Experimental + active comparator
IFX-1 + reduced dose GC
Drug: IFX-1
intravenously administered
Other Names:
  • CaCP29
Drug: Glucocorticoid (GC)
orally administered
Other Names:
  • Prednisone
Active Comparator: Group B Placebo + active comparator
Placebo-IFX-1 + standard dose GC
Drug: Glucocorticoid (GC)
orally administered
Other Names:
  • Prednisone
Drug: Placebo-IFX-1
intravenously administered
Other Names:
  • Placebo
Placebo Comparator: Group C Experimental + placebo comparator
IFX-1 + Placebo-GC
Drug: IFX-1
intravenously administered
Other Names:
  • CaCP29
Drug: Placebo-Glucocorticoid (Placebo-GC)
orally administered
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects Achieving Clinical Response
Time Frame: Baseline, Week 16
Efficacy Endpoint: Percentage of subjects achieving clinical response (reduction in Birmingham Vasculitis Activity Score version 3 [BVASv3] of ≥50% compared to baseline and no worsening in any body system). Subjects who received rescue therapy after Day 1 or discontinued due to related adverse event, lack of efficacy or progressive disease are considered as non-responders at all subsequent visits. The BVASv3 score ranges from 0 to 63 with higher values representing higher disease activity.
Baseline, Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With Clinical Remission
Time Frame: Week 16
Efficacy endpoint: Percentage of subjects with clinical remission, defined as having a BVASv3 = 0. Subjects who received rescue therapy after Day 1 or discontinued due to related adverse event, lack of efficacy or progressive disease are considered as non-responders at all subsequent visits. The BVASv3 score ranges from 0 to 63 with higher values representing higher disease activity.
Week 16
Change From Baseline in BVASv3 Total Score
Time Frame: Baseline, Week 16
Efficacy endpoint: Absolute Change from baseline (= screening assessment) in Birmingham Vasculitis Activity Score version 3 (BVASv3) total score; The BVASv3 score ranges from 0 to 63 with higher values representing higher disease activity. The total score is derived by summing up item scores according to the scoring manual for the BVASv3.
Baseline, Week 16
Vasculitis Damage Index (VDI)
Time Frame: Week 16
Efficacy endpoint: Absolute values of VDI; The VDI total score ranges from 0 to 64 with higher scores indicating more organ damage since the onset of vasculitis. The total score is the number of present damage items.
Week 16
Physician Global Assessment (PGA)
Time Frame: Week 16
Efficacy endpoint: Absolute values in PGA; Physician global assessment scale: 0 = Remission to 10 = Maximum activity;
Week 16
Estimated Glomerular Filtration Rate
Time Frame: Week 16

Efficacy endpoint: Absolute values of estimated glomerular filtration rate (eGFR) in mL/min/1.73 m²; The eGFR was calculated by the central laboratory according to the Modified Diet in Renal Disease equation:

eGFR = 175 x (serum creatinine, mg/dL)-1.154 x (age, years)-0.203 x (0.742 if female) x (1.212 if black)
Week 16
Number and Percentage of Subjects Who Had a Treatment-emergent Adverse Event (TEAE)
Time Frame: Week 24
Safety endpoint: Number and percentage of subjects who had a treatment-emergent adverse event (TEAE)
Week 24
Glucocorticoid Toxicity Index (GTI)
Time Frame: Week 16
Safety endpoint: The GTI total score ranges from -35 to 410 (because the bone domain is excluded in this study) with higher score indicating greater Glucocorticoid toxicity. Scoring was performed in the electronic case report form according to the corresponding scoring manual in "Development of a Glucocorticoid Toxicity Index (GTI) using multicriteria decision analysis." by Miloslavsky EM, Naden RP, Bijlsma JW, Brogan PA, Brown ES, Brunetta P, et al.
Week 16
IFX-1 Plasma Concentrations (Pre-dose)
Time Frame: Week 16 (pre-dose)
Pharmacokinetics endpoint: IFX-1 plasma concentrations assessed prior to study drug administration at corresponding visit.
Week 16 (pre-dose)
Plasma Concentrations of C5a
Time Frame: Week 16
Pharmacodynamics endpoint: Plasma concentrations of C5a
Week 16
IFX-1 Blocking Activity 10 nM
Time Frame: Week 16
Pharmacodynamics endpoint: IFX-1 blocking activity 10 nM
Week 16
IFX-1 Blocking Activity 2.5 nM
Time Frame: Week 16
Pharmacodynamics endpoint: IFX-1 blocking activity 2.5 nM
Week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

InflaRx GmbH

Investigators

  • Study Director: Anja Pfaff, PhD, InflaRx GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2019

Primary Completion (Actual)

April 14, 2021

Study Completion (Actual)

June 8, 2021

Study Registration Dates

First Submitted

March 8, 2019

First Submitted That Met QC Criteria

March 27, 2019

First Posted (Actual)

March 29, 2019

Study Record Updates

Last Update Posted (Actual)

August 25, 2022

Last Update Submitted That Met QC Criteria

August 3, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFX-1-P2.5

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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