Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)
Conditions
Interventions
Patients should visit the clinics and be willing to receive their study drug
comparator an/or placebo according to the dosing schema.
Furthermore their data of Medical history and demographic data wi
Sponsors
InflaRx GmbH
Eligibility
Age
18 Years to 99 Years
Inclusion 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 antiproteinase 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.
Exclusion criteria
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 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 prednisoneequivalent 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 Informati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Netherlands
Outcome results
None listed