A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.

Sanofi

Status and phase: Enrolling; Phase 3

Conditions: Secondary Progressive Multiple Sclerosis; Relapsing Multiple Sclerosis; Progressive Relapsing Multiple Sclerosis

Treatments: Drug: Teriflunomide; Drug: Placebo; Drug: Tolebrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06372145

U1111-1287-6797 (Registry Identifier)

LTS17043

2023-503631-18 (Registry Identifier)

Details and patient eligibility

About

This is a Phase 3 extension, global, multicenter study to assess the long-term safety and tolerability of tolebrutinib in adult participants (aged ≥18 years) with RMS, PPMS, or NRSPMS who were previously enrolled in the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 tolebrutinib pivotal trials (GEMINI 1 [EFC16033], GEMINI 2 [EFC16034], HERCULES [EFC16645], or PERSEUS [EFC16035]).

SUBSTUDY: ToleDYNAMIC substudy

Full description

Participants with relapsing MS from the Phase 2b LTS16004 parent study will continue open-label (OL) tolebrutinib.

All participants from the Phase 3 parent studies (EFC16033, EFC16034, EFC16645, and EFC16035) will learn which treatment they received in the parent study:

• If from one of the Phase 3 relapsing MS studies and on teriflunomide, an accelerated elimination procedure or a 3-month washout period is required prior to starting OL tolebrutinib. If on teriflunomide, and benefiting and recommended by the Investigator, the participant may opt to continue teriflunomide outside of the LTS17043 study, if clinically appropriate. If on tolebrutinib, the participant will continue tolebrutinib.
• All participants from one of the Phase 3 progressive MS studies will start OL tolebrutinib.
• If a participant already started OL tolebrutinib in the Phase 3 parent study this will be continued.
• 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.

The treatment duration per participant will be approximately 3 years of OL tolebrutinib.

Enrollment: 2,500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

• 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 38°C and clinically unstable), or recurring systemic infection, as judged by the Investigator
• 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.
• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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2,500 participants in 2 patient groups

Tolebrutinib

Experimental group

Description:

* 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.

Treatment:

Drug: Tolebrutinib

Drug: Placebo

Teriflunomide

Active Comparator group

Description:

* 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.

Treatment:

Drug: Teriflunomide

Drug: Placebo