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 objectives:*To assess safety and tolerability of IFX-1*To compare GC-induced toxicity of…
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Source
Brief title
Condition
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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.
Background summary
GPA and MPA most commonly occur in older adults, although these diseases have
been reported at all ages. The incidence of these conditions in the United
States of America is approximately 6,000 new cases per year, and the estimated
prevalence is 25,000 to 30,000 cases. The overall incidence rates of AAV in
Europe are reported to be in the range of 13 to approximately 20 per million.
Although treatment failures and disease relapses decreased due to the
improvement of remission-induction regimens during recent years, patients with
MPA and GPA treated with conventional regimens have a 9-fold increased
mortality risk in the first year attributed to infection, cardiovascular
disease, malignancies, vasculitis activity, and renal disease It is proven that
current therapies contribute to more than half of this increased risk rather
than the underlying disease itself. Most of the side effects are attributed to
the high-dose of GCs, which are still part of Standard of Care for MPA and GPA.
GCs have long-term side effects such as osteoporosis, Cushing*s syndrome,
increased infection risk and risk of diabetes mellitus , and progressive organ
damage. Therefore, the replacement of GCs by IFX-1 may improve the short- and
long-term safety of treatment of MPA and GPA for the induction of remission.
Study 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 objectives:
*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.
Study design
This is a prospective, randomized, double-blind, double-dummy,
active-controlled, multicenter, 2-part Phase II study evaluating the efficacy
of IFX-1 treatment in the replacement of GCs in subjects with GPA or MPA
Intervention
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 will be
collected They must undergo physicial and vital signs examinations. An
electrocardiogram will be made. Blood and urine will be collected.
Study burden and risks
In a pharmaceutical trial like this one, every risk or side effect cannot be
predicted. Each person's reaction to a test drug may be different.
The ability of IFX-1 to treat GPA/MPA in combination with immunosuppressive
therapy has not yet been demonstrated. Expected GC-related side effects are
fewer. Furthermore, the safety of IFX-1 has been investigated in 3 Phase II
studies, conducted in 48 subjects with early septic organ dysfunction treated
with IFX-1. Overall, IFX-1 was safe and well tolerated in all these studies,
and no additional risks associated with the administration of IFX-1 were
observed.
Because IFX-1 is an antibody/protein, a general risk for anaphylactic reactions
exists. Subjects who are included in this study are treated with IFX 1 at the
study site so that adequate treatment and care is available in case of an
anaphylactic reaction. To date, no anaphylactic reactions have been reported
after administration of IFX-1 in clinical Phase I and II studies. The
hypothesized benefit of treatment with IFX-1, therefore, outweighs the
potential risks for the subjects participating in this study.
Winzerlaer Str. 2
Jena 07745
DE
Winzerlaer Str. 2
Jena 07745
DE
Listed location countries
Age
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
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 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 subject might not comply with the
requirements of the study protocol.
20.The subject is an employee or direct relative of an employee of the sponsor
(InflaRx GmbH).
21.The subject is imprisoned or lawfully kept in an institution.
22.The subject has participated in an investigational clinical study during the
12 weeks (or 5 times the half-life of the previous IMP, whichever is longer)
before screening, or plans to participate in another investigational clinical
study during their participation in this study.
23.Male subjects with female partners of childbearing potential unwilling to
use contraception (condoms) during treatment and for at least 3 months after
last administration of IFX-1/Placebo-IFX-1.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR 2018-000768-2-NL |
| CCMO | NL67655.056.18 |