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

Phase 3

Active, not recruiting

Conditions: Nervous system diseases

Interventions: Drug: -

Registration Number: 2023-503631-18-01

Lead Sponsor: Sanofi-Aventis Recherche & Developpement

Brief Summary: To determine the long-term safety and tolerability of tolebrutinib in participants with relapsing multiple sclerosis (RMS) and progressive multiple sclerosis (PMS)

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 1405

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: Not specified

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
-	-	Participants receiving -

Primary Outcome Measures

Name	Time	Method
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 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		Number of Participants with Potentially clinically significant abnormalities (PCSAs

Secondary Outcome Measures

Name	Time	Method
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		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
Annualized Relapse Rate (ARR) for RMS only		Annualized Relapse Rate (ARR) for RMS only
Number of new and/or enlarging T2-hyperintense lesions per year		Number of new and/or enlarging T2-hyperintense lesions per year
Change from baseline in total volume of T2-hyperintense lesions		Change from baseline in total volume of T2-hyperintense lesions
ToleDYNAMIC substudy Change from baseline in biomarkers		ToleDYNAMIC substudy Change from baseline in biomarkers

Trial Locations

Locations (156): Latvijas Juras medicinas centrs AS
🇱🇻
Riga, Latvia
Pauls Stradins Clinical University Hospital
🇱🇻
Riga, Latvia
General University Hospital Of Larissa
🇬🇷
Larissa, Greece
Geniko Nosokomeio Thessalonikis George Papanikolaou
🇬🇷
Thessaloniki, Greece
Athens Medical Center S.A.
🇬🇷
Maroussi, Greece
Eginitio Hospital
🇬🇷
Athens, Greece
University General Hospital Of Thessaloniki Ahepa
🇬🇷
Thessaloniki, Greece
401 General Military Hospital Of Athens
🇬🇷
Athens, Greece
University General Hospital Attikon
🇬🇷
Athens, Greece
St. Luke's Hospital S.A.
🇬🇷
Thessaloniki, Greece
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Latvijas Juras medicinas centrs AS
🇱🇻Riga, Latvia
Jolanta Kanina
Site contact
0037167098417
jolanta@ljmc.lv