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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03895801
Recruitment Status : Completed
First Posted : March 29, 2019
Results First Posted : August 25, 2022
Last Update Posted : August 25, 2022
Sponsor:
Information provided by (Responsible Party):
InflaRx GmbH

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Granulomatosis With Polyangiitis (GPA) Microscopic Polyangiitis (MPA) Drug: IFX-1 Drug: Placebo-IFX-1 Drug: Glucocorticoid (GC) Drug: Placebo-Glucocorticoid (Placebo-GC) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : April 3, 2019
Actual Primary Completion Date : April 14, 2021
Actual Study Completion Date : June 8, 2021


Arm Intervention/treatment
Experimental: Group A Experimental + active comparator
IFX-1 + reduced dose GC
Drug: IFX-1
intravenously administered
Other Name: CaCP29

Drug: Glucocorticoid (GC)
orally administered
Other Name: Prednisone

Active Comparator: Group B Placebo + active comparator
Placebo-IFX-1 + standard dose GC
Drug: Placebo-IFX-1
intravenously administered
Other Name: Placebo

Drug: Glucocorticoid (GC)
orally administered
Other Name: Prednisone

Placebo Comparator: Group C Experimental + placebo comparator
IFX-1 + Placebo-GC
Drug: IFX-1
intravenously administered
Other Name: CaCP29

Drug: Placebo-Glucocorticoid (Placebo-GC)
orally administered
Other Name: Placebo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Physician Global Assessment (PGA) [ Time Frame: Week 16 ]
    Efficacy endpoint: Absolute values in PGA; Physician global assessment scale: 0 = Remission to 10 = Maximum activity;

  5. 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)


  6. 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)

  7. 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.

  8. 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.

  9. Plasma Concentrations of C5a [ Time Frame: Week 16 ]
    Pharmacodynamics endpoint: Plasma concentrations of C5a

  10. IFX-1 Blocking Activity 10 nM [ Time Frame: Week 16 ]
    Pharmacodynamics endpoint: IFX-1 blocking activity 10 nM

  11. IFX-1 Blocking Activity 2.5 nM [ Time Frame: Week 16 ]
    Pharmacodynamics endpoint: IFX-1 blocking activity 2.5 nM



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895801


Locations
Show Show 76 study locations
Sponsors and Collaborators
InflaRx GmbH
Investigators
Layout table for investigator information
Study Director: Anja Pfaff, PhD InflaRx GmbH
Principal Investigator: Peter A. Merkel, MD, MPH University of Pennsylvania
  Study Documents (Full-Text)

Documents provided by InflaRx GmbH:
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Responsible Party: InflaRx GmbH
ClinicalTrials.gov Identifier: NCT03895801    
Other Study ID Numbers: IFX-1-P2.5
First Posted: March 29, 2019    Key Record Dates
Results First Posted: August 25, 2022
Last Update Posted: August 25, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by InflaRx GmbH:
granulomatosis
polyangiitis
corticosteroid
replacement
glucocorticoid
Additional relevant MeSH terms:
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Systemic Vasculitis
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Granulomatosis with Polyangiitis
Microscopic Polyangiitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Autoimmune Diseases
Immune System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Prednisone
Glucocorticoids
Vilobelimab
Anti-Inflammatory Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors