A Randomized Open Label Trial Exploring the Soluble and Imaging Biomarker Dynamic Responses to Tolebrutinib Compared to Rituximab Treatment in Patients with Multiple Sclerosis (MS)

INTERVENTION: Product Name: Tolebrutinib, Product Code:PRD13214517, Pharmaceutical Form: FILM‐COATED TABLET, Other descriptive name: , Strength: , Product Name: , Product Code:SCP872361, Pharmaceutical Form: , Other descriptive name: , Strength: CONDITION: Multiple Sclerosis ; MedDRA version: 27.0Level: PTClassification code: 10080700Term: Relapsing multiple sclerosis Class: 100000004852 ; MedDRA version: 21.1Level: PTClassification code: 10070495Term: Multiple sclerosis relapse prophylaxis Class: 100000004865 Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To evaluate the change from baseline in cerebral spinal fluid (CSF) neurofilament light chain (NfL) in people with MS (pwMS) treated with Tolebrutinib following Rituximab treatment compared to pwMS remaining on Rituximab treatment. Primary end point(s): Relative change from baseline in CSF NfL at 12 months Secondary Objective: To assess the changes from baseline in soluble biomarkers associated with the innate immune system, axonal damage, immune cells recruitment to the CNS (chemoattractants), the complement system and synaptic integrity in pwMS treated with Tolebrutinib following Rituximab treatment compared to pwMS remaining on Rituximab treatment. SECONDARY OUTCOME: Secondary end point(s):CSF and serum GFAP at 12 and 24 months Secondary end point(s):CSF biomarkers of chemokines (CXCL10, CXCL13), innate immuny (LCN2, CHIT1), complement system (C1QA, C5), and synapses (SNAP25, SV2A) at 12 months Secondary end point(s):Serum NfL at 12 and 24 months INCLUSION CRITERIA: 1. The subject has given written informed consent to participate in the study., 10. Be willing and able to follow all study procedures and assessments according to the study protocol., 11. Female patients of childbearing potential (FPCBP) or procreative male patients (PMP), willing to use highly effective contraceptive methods throughout the study duration and at least until 5 months after the last study treatment., 2. Current diagnosis of MS, based on McDonald 2017 criteria., 3. Having received treatment with rituximab, as per local clinical routine for at least 24 months prior to the Screening Visit, with latest dose administered between 3 and 9 months prior Screening Visit., 4. Having expanded disability status scale (EDSS) 2 ‐6 inclusive at Screening., 5. Present clinical worsening in one or more neurological domains as assessed by EDSS, ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by SDMT or increased need of walking aids