Main objective:To demonstrate superior efficacy with evobrutinib compared to Teriflunomide in terms of Annualized Relapse Rate (ARR) Secondary objectives:a.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomide on disability…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
ARR based on qualified relapses at Week 96 in participants with RMS
Secondary outcome
a. Time to first occurrence of 12-week confirmed disability progression (CDP)
as measured by the Expanded Disability Status Scale (EDSS) over 96 weeks
b.Time to first occurrence of 24-week CDP as measured by EDSS over 96 weeks
c.Change from Baseline (CFB) in Patient Reported Outcomes Measurement
Information System [PROMIS] PF score at 96 weeks
d.CFB in PROMIS Fatigue score at 96 weeks
e.Total number of T1 Gd+ lesions based on assessments at Week 24, Week 48, and
Week 96.
f. Total number of new or enlarging T2 lesions based on assessments at Week 24,
Week 48, and Week 96
g.Safety as assessed by the nature, severity, and occurrence of adverse events
(AEs) and adverse events of special interest (AESIs); vital signs;
electrocardiograms (ECGs); absolute concentrations and change from Baseline in
immunoglobulin (Ig) levels; and clinical laboratory safety parameters up to
Week 108
h. OLE period:
*Efficacy and HRQoL endpoints at Weeks 48, 96, and 144
oARR, based on protocol-defined qualified relapses
oChange from Baseline in PROMIS PF score
oChange from Baseline in PROMIS fatigue score
oChange from Baseline in Medical Outcomes Study 36 Item Short Form Health
Survey (SF-36v2)
*Efficacy and HRQoL endpoints over 144 weeks
oTime to first occurrence of 12-week confirmed EDSS progression over 144 weeks
oTime to first occurrence of 24-week confirmed EDSS progression over 144 weeks
oTime to first occurrence of 12-week confirmed PF deterioration compared to
Baseline over 144 weeks
*Efficacy endpoints at Weeks 24, 48, 96, and 144
oTotal number of new or enlarging T2 lesions
oTotal number of T1 Gd+ lesions
*Safety as assessed by the nature, severity, and occurrence of AEs and AESIs;
vital signs; ECGs; absolute concentrations and change from Baseline in Ig
levels; clinical laboratory safety parameters up to Week 144
* Changes in fluid biomarker levels between treatment groups
* Correlations between levels in fluid biomarkers, gene expression and MRI
changes, and clinical outcomes measured by SDMT, EDSS, 9HPT,
T25-FW and relapses
Background summary
Currently there is no cure for MS, but the course of the disease can be altered
favorably with disease-modifying drugs (DMDs) with varying levels of efficacy,
and distinct safety and tolerability profiles. Despite the recent approvals of
newer therapies for the treatment of MS, there remains an unmet need for highly
effective and well-tolerated therapies for patients with MS at all stages of
the disease. Early treatment with a highly efficacious and safer DMD could be
advantageous for long term quality of life for MS patients and might slow the
process of brain atrophy, which accompanies axonal damage and loss of gray and
white matter. Since B cell depletion studies have shown that antibody
independent B cell functions play an important role in MS pathogenesis and an
altered innate immune system contributes to disability progression and repair
in MS, evobrutinib may offer advantages over current approved DMDs. Evobrutinib
is a highly specific, oral inhibitor of BTK that inhibits B cell activation and
B cell/T cell interaction, decreasing plasma cell formation and autoantibody
production.
Study objective
Main objective:
To demonstrate superior efficacy with evobrutinib compared to Teriflunomide in
terms of Annualized Relapse Rate (ARR)
Secondary objectives:
a.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomide
on disability progression
b.To demonstrate the efficacy of evobrutinib relative to that of Teriflunomide
on patient reported symptoms and functional status
c.To demonstrate the efficacy of evobrutinib relative to that of
Teriflunomideon magnetic resonance imaging (MRI) lesion parameters
d.To characterize the safety and tolerability of evobrutinib.
e. OLE period: To evaluate the long-term safety, efficacy, and HRQoL of
evobrutinib for an additional up to 144 weeks.
Study design
A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double
Dummy, Active Controlled Study in participants with relapsing multiple
sclerosis
Study burden and risks
Evobrutinib inhibits activation of B cells via the B cell receptor, decreasing
plasma cell formation and autoantibody production. Also, evobrutinib shows
inhibition of myeloid cell activation by immune complexes. In addition,
evobrutinib inhibits activation of myeloid cells by immune complexes via Fc
receptors as well as the differentiation of proinflammatory macrophages. Thus,
evobrutinib may be suitable for the treatment of multiple sclerosis (MS).
Considering the unmet medical need in MS patients, reduction of MS activities
(decreased in the number of Gd+ T1 lesions and lower ARR compared with
placebo), convenience of an oral therapy and the measures put in place to
mitigate the important identified and important potential risks, the
benefit-risk of evobrutinib 45 mg twice daily supports continued clinical
development of evobrutinib in this population.
Frankfurter Str. 250
Darmstadt 64293
DE
Frankfurter Str. 250
Darmstadt 64293
DE
Listed location countries
Age
Inclusion criteria
- 18 years to 55 years female and male participants
- Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis
[RRMS] or secondary progressive multiple sclerosis [SPMS] with relapses) in
accordance with 2017 Revised McDonald criteria
(Thompson 2018)
- Participants with one or more documented relapses within the 2 years before
Screening with either: a. one relapse which occurred within the last year prior
to randomization, OR b. the presence of at least 1
gadolinium-enhancing (Gd+) T1 lesion within 6 months prior to randomization
- Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5
at Screening and Baseline (Day 1). Participants with an EDSS score <<= 2 at
Screening and Baseline (Day 1) are only eligible for participation if their
disease duration (time since onset of symptoms) is no more than 10 years
- Participants are neurologically stable for ><= 30 days prior to both screening
and baseline
- Female participants must be neither pregnant nor breast-feeding or must lack
child-bearing potential (as defined by either: post-menopausal or surgically
sterile), or use an effective method of contraception for the duration of the
study and at least 2 years after study intervention due to the long elimination
period for teriflunomide of 2 years, unless the participant undergoes an
accelerated elimination procedure - Male participants must refrain from
donating sperm and/or abstain from intercourse with women of child-bearing
potential or use an effective method of contraception for the duration of the
study and at least 2 years after study intervention due to the long elimination
period for teriflunomide of 2 years, unless the participant undergoes an
accelerated elimination procedure
- Participants have given written informed consent prior to any study related
procedure
- Other protocol defined inclusion criteria could apply.
Exclusion criteria
- Participants diagnosed with Progressive MS, in accordance with the 2017
Revised McDonald criteria as follows: a). Participants with Primary Progressive
MS. b) Participants with secondary progressive MS without evidence of relapse.
- Disease duration more than (>) 10 years in participants with an EDSS =< 2.0
at screening.
- Immunologic disorder other than MS, or any other condition requiring oral,
intravenous (IV) , intramuscular, or intra-articular corticosteroid therapy,
with the exception of well-controlled Type 2 Diabetes mellitus or well
controlled thyroid disease.
-Other protocol defined exclusion criteria could apply.
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 | EUCTR2019-004972-20-NL |
| CCMO | NL73999.056.20 |