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)
- Conditions
- Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)10047066
- Registration Number
- NL-OMON55826
- Lead Sponsor
- InflaRx GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
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.
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 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the proportion of subjects achieving clinical<br /><br>response defined as reduction in BVASv3 * 50% at Week 16 compared to Baseline<br /><br>(= screening assessment) and no worsening in any body system. Subjects who<br /><br>receive rescue therapy until Week 16 will be considered as not having achieved<br /><br>clinical response.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1.Proportion of subjects with clinical response, defined as reduction in BVASv3<br /><br>* 50% and no worsening in any body system at each measurement time point except<br /><br>Week 16. Subjects who receive rescue therapy will be considered as not having<br /><br>achieved clinical response at each time point later than the first<br /><br>administration of rescue therapy<br /><br>2.Proportion of subjects with a clinical remission defined as having a BVASv3 =<br /><br>0 at Week 16<br /><br>3.Change from baseline (=screening assessment) in BVASv3 total score at Week 16<br /><br>4.Absolute values and absolute and relative change from Day 1 in the VDI at<br /><br>Week 16<br /><br>5.Absolute values and absolute and relative change from Day 1 in the PGA at<br /><br>Week 16<br /><br>6.Absolute values and absolute and relative change from Day 1 in eGFR in<br /><br>mL/min/1.73 m² at Week 16.</p><br>