RMS Study of BTK Inhibitor SAR442168

Relapsing Multiple Sclerosis Clinical Trial

Official title: A Phase 3, Randomed, Double-blind Efficacy and Safety Comparing SAR442168 and Terfluramide (Aubaglo®) in Particpants With Relapsing Forms of Multiple Sclerosis (GEMINI1)

Status Recruiting

Clinical Trial Summary

To access SAR442168 in the RMS populstion. Efficaty will be accessed by adjudicated relapse rate, disability progression, and MRI findings of disease activity.

Clinical Trial Description

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 B- or 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. ;

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

• NCT number: NCT04964791
• Study type: Observational
• Source: Peking University Third Hospital
• Status: Recruiting
• Start date: August 1, 2020
• Completion date: August 31, 2024