Clinical trial NCT03895801: Study of IFX-1 to Replace Steroids in Patients With Granulomatosis With Polyangiitis and Microscopic Polyangiitis.
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Granulomatosis With Polyangiitis (GPA)
Microscopic Polyangiitis (MPA)
Keywords: granulomatosis
polyangiitis
corticosteroid
replacement
glucocorticoid
Lead sponsor: InflaRx GmbH
Sponsor class: INDUSTRY
First posted: 2019-03-29
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Subjects Achieving Clinical Response
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Percentage of Subjects With Clinical Remission
timeFrame: Week 16
measure: Change From Baseline in BVASv3 Total Score
timeFrame: Baseline, Week 16
measure: Vasculitis Damage Index (VDI)
timeFrame: Week 16
measure: Physician Global Assessment (PGA)
timeFrame: Week 16
measure: Estimated Glomerular Filtration Rate
timeFrame: Week 16
measure: Number and Percentage of Subjects Who Had a Treatment-emergent Adverse Event (TEAE)
timeFrame: Week 24
measure: Glucocorticoid Toxicity Index (GTI)
timeFrame: Week 16
measure: IFX-1 Plasma Concentrations (Pre-dose)
timeFrame: Week 16 (pre-dose)
measure: Plasma Concentrations of C5a
timeFrame: Week 16
measure: IFX-1 Blocking Activity 10 nM
timeFrame: Week 16
measure: IFX-1 Blocking Activity 2.5 nM
timeFrame: Week 16
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Clinical Site
city: Liège
country: Belgium
facility: Clinical Site
city: Hradec Králové
country: Czechia
facility: Clinical Site
city: Prague
country: Czechia
facility: Clinical Site
city: Praha
country: Czechia
facility: Clinical Site
city: Praha
country: Czechia
facility: Clinical Site
city: Angers
country: France
facility: Clinical Site
city: Brest
country: France
facility: Clinical Site
city: Créteil
country: France
facility: Clinical Site
city: Grenoble
country: France
facility: Clinical Site
city: Lille
country: France
facility: Clinical Site
city: Montpellier
country: France
facility: Clinical Site
city: Paris
country: France
facility: Clinical Site
city: Paris
country: France
facility: Clinical Site
city: Paris
country: France
facility: Clinical Site
city: Pessac
country: France
facility: Clinical Site
city: Poitiers
country: France
facility: Clinical Site
city: Jena
country: Germany
facility: Clinical Site
state: Thüringen
city: Aachen
country: Germany
facility: Clinical Site
city: Berlin
country: Germany
facility: Clinical Site
city: Dresden
country: Germany
facility: Clinical Site
city: Essen
country: Germany
facility: Clinical Site
city: Freiburg
country: Germany
facility: Clinical Site
city: Hannover
country: Germany
facility: Clinical Site
city: Kirchheim unter Teck
country: Germany
facility: Clinical Site
city: Köln
country: Germany
facility: Clinical Site
city: Leipzig
country: Germany
facility: Clinical Site
city: Ludwigshafen
country: Germany
facility: Clinical Site
city: Mannheim
country: Germany
facility: Clinical Site
city: Münster
country: Germany
facility: Clinical Site
city: Stuttgart
country: Germany
facility: Clinical Site
city: Catania
country: Italy
facility: Clinical Site
city: Lecco
country: Italy
facility: Clinical Site
city: Messina
country: Italy
facility: Clinical Site
city: Milano
country: Italy
facility: Clinical Site
city: Milano
country: Italy
facility: Clinical Site
city: Monza
country: Italy
facility: Clinical Site
city: Pavia
country: Italy
facility: Clinical Site
city: Pisa
country: Italy
facility: Clinical Site
city: Verona
country: Italy
facility: Clinical Site
city: Maastricht
country: Netherlands
facility: Clinical Site
city: Rotterdam
country: Netherlands
facility: Clinical Site
city: Kemerovo
country: Russian Federation
facility: Clinical Site
city: Moscow
country: Russian Federation
facility: Clinical Site
city: Moscow
country: Russian Federation
facility: Clinical site
city: Moscow
country: Russian Federation
facility: Clinical site
city: Orenburg
country: Russian Federation
facility: Clinical Site
city: Petrozavodsk
country: Russian Federation
facility: Clinical Site
city: Saratov
country: Russian Federation
facility: Clinical site
city: Saratov
country: Russian Federation
facility: Clinical Site
city: Yaroslavl
country: Russian Federation
facility: Clinical Site
city: Alcorcón
country: Spain
facility: Clinical Site
city: Badalona
country: Spain
facility: Clinical Site
city: Barcelona
country: Spain
facility: Clinical Site
city: Barcelona
country: Spain
facility: Clinical site
city: Barcelona
country: Spain
facility: Clinical Site
city: Fuenlabrada
country: Spain
facility: Clinical Site
city: L'Hospitalet De Llobregat
country: Spain
facility: Clinical Site
city: Sevilla
country: Spain
facility: Clinical Site
city: Sevilla
country: Spain
facility: Clinical Site
city: Sevilla
country: Spain
facility: Clinical Site
city: Göteborg
country: Sweden
facility: Clinical Site
city: Stockholm
country: Sweden
facility: Clinical Site
city: Uppsala
country: Sweden
facility: Clinical Site
city: Saint Gallen
country: Switzerland
facility: Clinical Site
city: Zuerich
country: Switzerland
facility: Clinical Site
city: Aberdeen
country: United Kingdom
facility: Clinical Site
city: Cambridge
country: United Kingdom
facility: Clinical Site
city: Cardiff
country: United Kingdom
facility: Clinical Site
city: Leicester
country: United Kingdom
facility: Clinical Site
city: London
country: United Kingdom
facility: Clinical Site
city: London
country: United Kingdom
facility: Clinical Site
city: Portsmouth
country: United Kingdom
facility: Clinical Site
city: Preston
country: United Kingdom
facility: Clinical Site
city: Reading
country: United Kingdom
facility: Clinical Site
city: Sheffield
country: United Kingdom
facility: Clinical Site
Study officials:
affiliation: InflaRx GmbH
name: Anja Pfaff, PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Peter A. Merkel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: