Primary: to determine the long-term safety and tolerability of SAR442168 in RMS participants. Secondary: to evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods.
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events (AEs), serious adverse events (SAEs), safety findings on
magnetic resonance imaging (MRI), potentially clinically significant
abnormalities (PCSAs) in laboratory tests, electrocardiogram (ECG), or vital
signs during the study period.
Secondary outcome
- Number of new gadolinium (Gd)-enhancing T1-hyperintense lesions by brain MRI
- Number of new or enlarging T2 lesions
- Total number of Gd-enhancing T1-hyperintense lesions
- Number of relapses (annualized relapse rate [ARR]) during the study period
- Change in Expanded Disability Status Scale (EDSS) score from baseline over
time
Background summary
The Bruton's tyrosine kinase (BTK) pathway is critical to signaling in B
lymphocytes and myeloid cells including central nervous system (CNS) microglia.
Each of these cell types has been implicated in the pathophysiology of multiple
sclerosis (MS). Accordingly, SAR442168, a CNS-penetrant BTK inhibitor has the
potential for a dual mechanism of action by inhibiting antigen-induced B-cell
activation responsible for inflammation and by modulating maladaptive
microglial cells linked to neuroinflammation in the brain and spinal cord.
There is still a significant unmet need for therapies that target
neuroinflammation in the CNS with a goal of halting long term disability and
neurodegeneration in people with relapsing multiple sclerosis (RMS), and also
in progressive forms of the disease (primary progressive multiple sclerosis
[PPMS] and secondary progressive multiple sclerosis SPMS]). Even the most
recent high-efficacy disease-modifying therapies act mainly on adaptive
immunity in the periphery with only modest or temporary ability to halt
neuroinflammatory and neurodegenerative processes and stop disease progression,
as also demonstrated by recent studies in progressive MS.
Study objective
Primary: to determine the long-term safety and tolerability of SAR442168 in RMS
participants.
Secondary: to evaluate efficacy of SAR442168 on disease activity, assessed by
clinical and imaging methods.
Study design
A long-term, phase 2, Single Group Treatment study for participants previously
treated in the DRI15928 study. It consists of 2 parts: Part A, which is blinded
for participants and Investigators during the double-blind period of the study,
and Part B which is an open-label period of the study.
Intervention
Bruton's tyrosine kinase inhibitor. In phase A of the study the patient
receives a maximum of four tablets per day to achieve a daily dose of 5, 15, 30
or 60 mg, depending on the arm to which the patient was randomized in the
previous DRI15928 study. This is given in tablet form and the route of
administration is oral. In phase B of the study the patient will be transferred
to the optimal dose of SAR442168, 60mg, as determined from the DRI15928, and
the study will be open-label.
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events of study medication.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
- Participants must have completed treatment in the DRI15928 study
- Female participants must continue to use an acceptable effective
contraception method of birth control from inclusion and until the last study
dose, except if she has undergone sterilization at least 3 months earlier or is
postmenopausal.
Exclusion criteria
-The participant has a confirmed concomitant laboratory or ECG abnormality or
medical condition
deemed by the investigator incompatible with continuation of SAR442168
treatment.
-The participant has received any live (attenuated) vaccine (including but not
limited to varicella
zoster, oral polio, and nasal influenza) between the last DRI15928 visit and
the first treatment visit
in the LTS16004 study.
-The participant has received a non-study MS disease modifying treatment
between the last IMP
treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement
of the
Investigator may add unjustified risk to switching back and continuing
trreatment with SAR442168.
Washout periods after treatment with non-study DMTs should be respected except
for interferons or
glatiramer acetate treatment.
-The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8
hepatic enzymes.
Note: Such drugs need to be stopped at least 5 half-lives before study drug
administration.
The participant is receiving anticoagulant/antiplatelet therapies, including:
• Acetylsalicylic acid (aspirin)
• Antiplatelet drugs (eg, clopidogrel)
• Warfarin (vitamin K antagonist)
• Heparin, including low molecular weight heparin (antithrombin agents)
• Dabigatran (direct thrombin inhibitor)
• Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors)
Note: All above drugs need to be stopped at least 5 half-lives before study
drug administration
except for aspirin, which needs to be stopped at least 8 days beforehand.
-Prior/concurrent clinical study experience
-The participant is taking part in another interventional clinical trial of
another drug substance.
-Uncooperative behavior or any condition that could make the participant
potentially non-adherent
with the study procedures
Design
Recruitment
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 | EUCTR2018-004731-76-NL |
| CCMO | NL68933.029.19 |
| Other | U1111-1223-4256 |