Efficacy and safety study of a monoclonal antibody to replace steroids for treatment of patients with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) diseases.

• Register: EUCTR
• Last refreshed on: 26 July 2021
• Main ID: EUCTR2018-000768-27-NL
• Date of registration: 20/12/2018
• Prospective Registration: Yes
• Primary sponsor: InflaRx GmbH
• Public title: Efficacy and safety study of a monoclonal antibody to replace steroids for treatment of patients with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) diseases.
• Scientific 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)
• Date of first enrolment: 10/03/2019
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000768-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Double dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Czechia, Denmark, France, Germany, Italy, Netherlands, Russian Federation, Spain, Sweden, United Kingdom

Contacts

• Name: InflaRx GmbH
• Affiliation: InflaRx GmbH

• Name: InflaRx GmbH
• Affiliation: InflaRx GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, = 18 years of age.
2. Written informed consent obtained from subject.
3. Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference (CHCC).
4.History of positive antigen-specific ANCA testing since the time of diagnosis or at screening, or documented evidence of either anti-proteinase 3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) (for newly diagnosed subjects a recent positive antigen-specific ANCA testing is mandatory for inclusion)
5. Have = 1 “major” item, or = 3 other items, or = 2 renal items on the Birmingham Vasculitis Activity Score Version 3 (BVASv3).
6. Newly diagnosed or relapsed GPA or MPA that requires treatment with CYC or RTX plus GCs.
7. Estimated glomerular filtration rate (eGFR) = 20 mL/min/1.73 m².

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
Subjects who fulfil any of the following criteria at screening are not eligible to participate in the study:
1.Any other multi-system autoimmune disease as listed in Appendix 18.4.
2.Require mechanical ventilation because of alveolar hemorrhage at screening.
3.Known hypersensitivity to any investigational medicinal product (IMP) (i.e. GC, IFX-1) and/or any excipients.
4.Subject with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
5.Have required management of infections, as follows:
a.Chronic infection requiring anti-infective therapy (such as latent tuberculosis, pneumocystis, aspergillosis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria) within 3 months before screening.
b.Use of intravenous antibacterials, antivirals, anti-fungals, or anti parasitic agents within 30 days of screening.
6.Current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence.
7.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.
8.Any of the following abnormal laboratory findings at screening:
a.White blood cells < 3,500/mm3
b.Platelet count < 100,000/mm3
c.Transaminase values (AST and/or ALT) = 2.5 times the upper limit of normal range (ULN)
d.Total bilirubin = 1.5 times ULN
e.Alkaline Phosphatase (ALP) > 3 times ULN
9.Current or history of malignancy, lymphoproliferative, or myeloproliferative disorder except squamous cell or basal cell carcinomas of the skin and cervical carcinoma in situ with curative surgical treatment.
10.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.; If subject is on AZA, MMF or MPS or MTX, these drugs must be discontinued prior to receiving the first dose of CYC or RTX.
11.Received > 3 g cumulative intravenous GCs within 4 weeks before screening (RTX intravenous GC premedication is separate and does not
count to the 3 g).
12.a.Received an oral daily dose of a GC of > 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening.
b.Received an oral daily dose of a GC of > 80 mg prednisone equivalent within 2 weeks before screening.
13.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 renal dialysis within 12 weeks before screening.
14.Received a live vaccination within 4 weeks before screening or planned between screening and Week 2774.
15.Either active or latent tuberculosis treatment is ongoing.
16.Pregnant or lactating.
17.Clinically significant abnormal electrocardiogram (ECG) during screening.
18.Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception (pearl index < 1) during treatment and for at least 3 months after last administration of IFX-1/Placebo-IFX-1 (or up to 12 months, the timeframes for Standard of Care agents have to be considered as described in the respective Prescribing Information/SPCstimeframes). Contraception methods regarded as highly effective methods and the duration of contraception are further described in Section 7.7.
19.Evidence or suspicion that the s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Active Granulomatosis with Polyangiitis (Wegener’s) (GPA) and Microscopic Polyangiitis (MPA)
MedDRA version: 21.1 Level: PT Classification code 10063344 Term: Microscopic polyangiitis System Organ Class: 10047065 - Vascular disorders
MedDRA version: 21.1 Level: PT Classification code 10072579 Term: Granulomatosis with polyangiitis System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Product Name: IFX-1
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Vilobelimab
Current Sponsor code: IFX-1 (former code: CaCP29)
Other descriptive name: chimeric monoclonal antibody, IgG4 subtype
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: PredniSONE Tablets, USP
Product Name: Glucocorticoids (GC)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-10
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: GALEN® tablet
Product Name: Glucocorticoids (GC)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-10
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 16

Primary end point(s): The primary efficacy endpoint is the proportion of subjects achieving clinical response defined as reduction in BVASv3 = 50% at Week 16 compared to Baseline (= screening assessment) and no worsening in any body system. Subjects who receive rescue therapy until Week 16 will be considered as not having achieved clinical response.

Main Objective: The primary objective is to evaluate the efficacy of IFX-1 treatment as a replacement for glucocorticoids [GC] therapy in subjects with GPA and MPA.

Secondary Objective: •To assess safety and tolerability of IFX-1
•To compare GC-induced toxicity of standard-dose GC and reduced dose GC with IFX-1 treatment
•To generate data for PK and PD modelling of IFX-1 treatment.

Secondary Outcome(s)

Secondary end point(s): 1.Proportion of subjects with clinical response, defined as reduction in BVASv3 = 50% and no worsening in any body system at each measurement time point except Week 16. Subjects who receive rescue therapy will be considered as not having achieved clinical response at each time point later than the first administration of rescue therapy
2.Proportion of subjects with a clinical remission defined as having a BVASv3 = 0 at Week 16
3. Change from baseline (=screening assessment) in BVASv3 total score at Week 16
4.Absolute values and absolute and relative change from Day 1 in the VDI at Week 16
5.Absolute values and absolute and relative change from Day 1 in the PGA at Week 16
6.Absolute values and absolute and relative change from Day 1 in eGFR in mL/min/1.73 m² at Week 16.

Timepoint(s) of evaluation of this end point: 1. At weeks 0 (Day 1), 1, 2, 4, 8, 12, 20, 24
2. Week 16
3. 4. and 5. From Day 1 to week 16

Secondary ID(s)

2018-000768-27-CZ

IFX-1-P2.5

Source(s) of Monetary Support

InflaRx GmbH

Ethics review

Status: Approved
Approval date: 10/03/2019
Contact: