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

Microscopic Polyangiitis (MPA) Clinical Trial

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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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03895801
• Other study ID #: IFX-1-P2.5
• Status: Completed
• Phase: Phase 2
• Start date: April 3, 2019
• Est. completion date: June 8, 2021

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: June 8, 2021
• Est. primary completion date: April 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• IFX-1
intravenously administered
• Placebo-IFX-1
intravenously administered
• Glucocorticoid (GC)
orally administered
• Placebo-Glucocorticoid (Placebo-GC)
orally administered

Locations

Country	Name	City	State
Belgium	Clinical Site	Leuven
Belgium	Clinical Site	Liège
Czechia	Clinical Site	Hradec Králové
Czechia	Clinical Site	Prague
Czechia	Clinical Site	Praha
Czechia	Clinical Site	Praha
France	Clinical Site	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	Clinical Site	Paris
France	Clinical Site	Paris
France	Clinical Site	Pessac
France	Clinical Site	Poitiers
Germany	Clinical Site	Aachen
Germany	Clinical Site	Berlin
Germany	Clinical Site	Dresden
Germany	Clinical Site	Essen
Germany	Clinical Site	Freiburg
Germany	Clinical Site	Hannover
Germany	Clinical Site	Jena	Thüringen
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
Italy	Clinical Site	Catania
Italy	Clinical Site	Lecco
Italy	Clinical Site	Messina
Italy	Clinical Site	Milano
Italy	Clinical Site	Milano
Italy	Clinical Site	Monza
Italy	Clinical Site	Pavia
Italy	Clinical Site	Pisa
Italy	Clinical Site	Verona
Netherlands	Clinical Site	Maastricht
Netherlands	Clinical Site	Rotterdam
Russian Federation	Clinical Site	Kemerovo
Russian Federation	Clinical Site	Moscow
Russian Federation	Clinical site	Moscow
Russian Federation	Clinical site	Moscow
Russian Federation	Clinical Site	Orenburg
Russian Federation	Clinical Site	Petrozavodsk
Russian Federation	Clinical site	Saratov
Russian Federation	Clinical Site	Saratov
Russian Federation	Clinical Site	Yaroslavl
Spain	Clinical Site	Alcorcón
Spain	Clinical Site	Badalona
Spain	Clinical Site	Barcelona
Spain	Clinical site	Barcelona
Spain	Clinical Site	Barcelona
Spain	Clinical Site	Fuenlabrada
Spain	Clinical Site	L'Hospitalet De Llobregat
Spain	Clinical Site	Sevilla
Spain	Clinical Site	Sevilla
Spain	Clinical Site	Sevilla
Sweden	Clinical Site	Göteborg
Sweden	Clinical Site	Stockholm
Sweden	Clinical Site	Uppsala
Switzerland	Clinical Site	Saint Gallen
Switzerland	Clinical Site	Zuerich
United Kingdom	Clinical Site	Aberdeen
United Kingdom	Clinical Site	Cambridge
United Kingdom	Clinical Site	Cardiff
United Kingdom	Clinical Site	Leicester
United Kingdom	Clinical Site	London
United Kingdom	Clinical Site	London
United Kingdom	Clinical Site	Portsmouth
United Kingdom	Clinical Site	Preston
United Kingdom	Clinical Site	Reading
United Kingdom	Clinical Site	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
InflaRx GmbH

Countries where clinical trial is conducted

Belgium,  Czechia,  France,  Germany,  Italy,  Netherlands,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Achieving Clinical Response	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	Percentage of Subjects With Clinical Remission	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
Secondary	Change From Baseline in BVASv3 Total Score	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
Secondary	Vasculitis Damage Index (VDI)	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
Secondary	Physician Global Assessment (PGA)	Efficacy endpoint: Absolute values in PGA; Physician global assessment scale: 0 = Remission to 10 = Maximum activity;	Week 16
Secondary	Estimated Glomerular Filtration Rate	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
Secondary	Number and Percentage of Subjects Who Had a Treatment-emergent Adverse Event (TEAE)	Safety endpoint: Number and percentage of subjects who had a treatment-emergent adverse event (TEAE)	Week 24
Secondary	Glucocorticoid Toxicity Index (GTI)	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
Secondary	IFX-1 Plasma Concentrations (Pre-dose)	Pharmacokinetics endpoint: IFX-1 plasma concentrations assessed prior to study drug administration at corresponding visit.	Week 16 (pre-dose)
Secondary	Plasma Concentrations of C5a	Pharmacodynamics endpoint: Plasma concentrations of C5a	Week 16
Secondary	IFX-1 Blocking Activity 10 nM	Pharmacodynamics endpoint: IFX-1 blocking activity 10 nM	Week 16
Secondary	IFX-1 Blocking Activity 2.5 nM	Pharmacodynamics endpoint: IFX-1 blocking activity 2.5 nM	Week 16