A study to investigate long-term safety and tolerability of tolebrutinib in participants with multiple sclerosis

Phase 1

Recruiting

Conditions: ervous system diseases
MedDRA version: 21.1Level: PTClassification code: 10063400Term: Secondary progressive multiple sclerosis Class: 100000004852
MedDRA version: 21.1Level: PTClassification code: 10067063Term: Progressive relapsing multiple sclerosis Class: 100000004852
MedDRA version: 21.0Level: PTClassification code: 10080700Term: Relapsing multiple sclerosis Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: CTIS2023-503631-18-01

Lead Sponsor: Sanofi-Aventis Research & Development

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 2666

Inclusion Criteria

Participants with RMS, PPMS, or NRSPMS who completed the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 pivotal tolebrutinib trials (EFC16033, EFC16034, EFC16645, EFC16035) on IMP., OR - The Phase 2b LTS (LTS16004) or Phase 3 tolebrutinib pivotal trial participants who temporarily discontinued IMP due to a national emergency and completed the trial visits., ToleDYNAMIC Substudy: Inclusion criteria are those of the main study

Exclusion Criteria

The participant is at risk for or has a persistent chronic, active (including fever higher than 38°C and clinically unstable), or recurring systemic infection, as judged by the Investigator, The participant is receiving treatment during the study period with drugs not permitted by the study protocol, including potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes., ToleDYNAMIC Substudy: Exclusion criteria are those of the main study, For participants initiating OL tolebrutinib in the LTS17043 study: Participants at risk of developing or having reactivation of hepatitis, ie, results at the unblinding visit (RMS) or opt-in visit (PMS) for serological markers for hepatitis B and C viruses indicating acute or chronic infection, Active alcohol use disorder or a history of alcohol or drug abuse within 1 year prior to the opt-in visit, Current alcohol intake equal to or exceeding the following at the opt-in visit: more than 2 drinks per day for men and more than 1 drink per day for women, Abnormal ECG during the opt-in visit considered in the Investigator’s judgment to be clinically significant, such as QTcF >500 msec, in the context of this study., A bleeding disorder, known platelet dysfunction, abnormal platelet count (<100,000/microliter), history of significant bleeding event or other conditions and planned procedures that may predispose the participant to excessive bleeding during the study, as judged by the Investigator., For participants initiating OL tolebrutinib in the LTS17043 study: Confirmed unblinding visit (RMS) or opt-in visit (PMS) alanine aminotransferase (ALT) more than 1.5 × upper limit of normal (ULN) OR aspartate aminotransferase (AST) more than 1.5 × ULN OR alkaline phosphatase more than 2 × ULN (unless caused by non-liver-related disorder or explained by a stable chronic liver disorder) OR total bilirubin more than 1.5 × ULN (unless due to Gilbert syndrome or non-liver-related disorder)., Acute liver disease, cirrhosis, chronic liver disease (unless considered stable for more than 6 months)., Participants who developed clinically relevant cardiovascular, hepatic, endocrine, neuropsychiatric or other major systemic disease making implementation of the protocol or interpretation of the trial results difficult or that would put the patient at risk by participating in the trial, as judged by the Investigator.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the long-term safety and tolerability of tolebrutinib in participants with relapsing multiple sclerosis (RMS) and progressive multiple sclerosis (PMS);Secondary Objective: To assess long-term efficacy of open label (OL) tolebrutinib on disability progression, relapse rate (only in participants with RMS), and magnetic resonance imaging (MRI) parameters in participants with RMS and PMS;Primary end point(s): Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs leading to permanent study intervention discontinuation, Number of Participants with Potentially clinically significant abnormalities (PCSAs

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Time to onset of 6-month confirmed disability worsening (CDW for RMS) or confirmed disability progression (CDP for PPMS and NRSPMS) for participants from pivotal studies;Secondary end point(s):Annualized Relapse Rate (ARR) for RMS only;Secondary end point(s):Number of new and/or enlarging T2-hyperintense lesions per year;Secondary end point(s):Change from baseline in total volume of T2-hyperintense lesions;Secondary end point(s):ToleDYNAMIC substudy Change from baseline in biomarkers

Related Trials