To access SAR442168 in the RMS populstion. Efficaty will be accessed by adjudicated relapse
rate, disability progression, and MRI findings of disease activity.
Despite a number of disease-modifying therapies (DMTs) approved for relapsing multiple
sclerosis (RMS), there is still a need for additional efficacious treatments, especially
treatments that target disease mechanisms in the central nervous system (CNS) behind a closed
or partially closed blood-brain barrier. Current treatments cannot ensure long-term
suppression of multiple sclerosis (MS) inflammatory activity including relapse and new
magnetic resonance imaging (MRI) lesion control. Some medications delay RMS progression, but
the disease may still not be completely controlled, and it affects life activities and
wellbeing. Even the most recent high-efficacy DMTs mainly act on adaptive immunity in the
periphery with only modest ability to slow neuroinflammatory and neurodegenerative processes,
as demonstrated by recent studies in progressive MS. Therefore, development of MS treatments
with new modes of action is of interest. In addition to the current focus on suppressing Bor
T-cell mediated immunity in MS treatments, there is mounting evidence that innate
immunity, including myeloid lineage bone-marrow-derived monocytes, macrophages, and
CNS-resident microglial cells, is responsible for many of the neurodegenerative aspects of
MS. Modulation of innate immunity could therefore provide additional benefit in treatment of
MS. SAR442168 shows in vitro capacity to inhibit Bruton's tyrosine kinase (BTK), which is
responsible for downstream signaling in macrophages and microglial cells and is expected to
act on these targets in the brain due to its ability to penetrate the blood-brain barrier.
Based on this knowledge of the mode of action of SAR442168, its ability to penetrate the
blood-brain barrier, and available evidence from nonclinical and healthy volunteer studies,
SAR442168 is expected to prove itself as a high-efficacy disease-modifying treatment for MS.
The ability of SAR442168 to reduce formation of new, active brain lesions in MS was assessed
in a Phase 2b dose-finding trial in participants with RMS (DRI15928). This radiographic
outcome has been established as a highly reliable predictive biomarker for clinical efficacy
in pivotal studies in MS including Phase 3 RMS studies. The dose selected on the basis of the
SAR442168 effect on gadolinium-(Gd) enhancing T1-hyperintense lesions on MRI in the Phase 2b
trial will be used for this and other Phase 3 trials with SAR442168 in MS. The goal of this
Phase 3 study is to assess SAR442168 in the RMS population. Efficacy will be assessed by
adjudicated relapse rate, disability progression, and MRI findings of disease activity
VV-CLIN-0579239 1.0Amended Clinical Trial Protocol 01 07-May-2020 SAR442168-EFC16033 Version
number: 1 Property of the Sanofi group - strictly confidential Page 12 (Gd-enhancing lesions
and new/enlarging T2-hyperintense lesions). Together with evaluation of other secondary and
exploratory endpoints, this study will provide a comprehensive evaluation of the efficacy and
safety of SAR442168 in the RMS population.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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