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

JRCT ID: jRCT2031240058

Registered date:27/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Relapsing / Secondary progressive / Primary progressive multiple sclerosis
• Date of first enrollment: 03/06/2024
• Target sample size: 2500
• Countries of recruitment: TBD,Japan
• Study type: Interventional

Intervention(s)

Drug: SAR442168 (tolebrutinib)
Pharmaceutical form: Tablet, Route of administration: oral
Drug: Teriflunomide
Pharmaceutical form: Tablet, Route of administration: oral
Drug: Placebo
Pharmaceutical form: Tablet, Route of administration: oral

Arm description:
Experimental: Tolebrutinib
- Participants will receive OL tolebrunitib 60 mg once daily.
- RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study.

Active Comparator: Teriflunomide
- participants will receive teriflunomide 14 mg daily.
- RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment (either tolebrutinib or teriflunomide) as per their randomization from the parent study.
If unblinded to teriflunomide parent study treatment assignment, these RMS participants will continue teriflunomide in the LTS17043 study.

Outcome(s)

Primary Outcome

1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs leading to permanent study intervention discontinuation
[Time frame: From baseline until the End of study approximately 3 years per participant]
2. Number of Participants with Potentially clinically significant abnormalities (PCSAs)
[Time frame: From baseline until the End of study approximately 3 years per participant]
PCSAs determined by laboratory tests, ECG, or vital signs and safety findings on magnetic resonance imaging (MRI) during the study period.

Secondary Outcome

1. Time to onset of 6-month confirmed disability worsening (confirmed disability worsening [CDW] for RMS) or confirmed disability progression (confirmed disability progression [CDP] for PPMS and NRSPMS) for participants from pivotal studies
[Time frame: From baseline until the End of study approximately 3 years per participant]
Time to onset is defined as a sustained increase from baseline Expanded Disability Status Scale (EDSS) (pivotal trial) of:
- RMS: >=1.5 points when the baseline score is 0, >=1.0 point when the baseline score is 0.5 to =<5.5 or >=0.5 point when the baseline score is >5.5
- PPMS: >=1.0 point when the baseline score is =<5.5 or >=0.5 point when the baseline score is >5.5
- NRSPMS: >=1.0 point when the baseline score is =<5.0 or >=0.5 point when the baseline score is >5.0
2. Annualized Relapse Rate (ARR) for RMS only
[Time frame: From baseline until the End of study approximately 3 years per participant]
ARR during the OL treatment period assessed by confirmed protocol-defined relapses
3. Number of new and/or enlarging T2-hyperintense lesions per year
[Time frame: From baseline until the End of study approximately 3 years per participant]
4. Change from baseline in total volume of T2-hyperintense lesions
[Time frame: From baseline until the End of study approximately 3 years per participant]
5.ToleDYNAMIC substudy: Change from baseline in biomarkers
[Time frame: From baseline until 12 months per participant]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participants with relapsing multiple sclerosis (RMS), primary progressive multiple sclerosis (PPMS), or nonrelapsing secondary progressive multiple sclerosis (NRSPMS) who completed the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 pivotal tolebrutinib trials (EFC16033, EFC16034, EFC16645, EFC16035) on investigational medicinal product (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.

Immunological substudy (ToleDYNAMIC Substudy): Inclusion criteria are those of the main study.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- The participant is at risk for or has a persistent chronic, active (including fever higher than 38C and clinically unstable), or recurring systemic infection, as judged by the Investigator.
- For participants initiating open-label (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 (progressive multiple sclerosis [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 electrocardiogram (ECG) during the opt-in visit considered in the Investigator's judgment to be clinically significant, such as QT interval corrected using Fridericia's formula (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 x upper limit of normal (ULN) OR aspartate aminotransferase (AST) more than 1.5 x ULN OR alkaline phosphatase more than 2 x ULN (unless caused by non-liver-related disorder or explained by a stable chronic liver disorder) OR total bilirubin more than 1.5 x 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.
- 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.

NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

ToleDYNAMIC Substudy: Exclusion criteria are those of the main study.

Related Information

• Primary Sponsor: Tanaka Tomoyuki