Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis

NCT03996291 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: LTS16004U1111-1223-42562018-004731-76
• Study Type: interventional
• Target: 125
• Locations: 8 countries
• Sites: 32

Brief Summary

Primary Objective: To determine the long-term safety and tolerability of SAR442168 in RMS participants Secondary Objective: To evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the respective on-treatment periods.

  From first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B

Secondary Outcomes (5)

• Mean Number of New Gadolinium (Gd)-Enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192

  Weeks 192 and 240

• Mean Number of New or Enlarging T2 Lesions at Week 240 Relative to Week 192

  Weeks 192 and 240

• Total Mean Number of Gd-enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192

  Weeks 192 and 240

• Annualized Relapse Rate (ARR)

  From Baseline (enrollment in LTS16004, Day 1) to Week 240

• Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 240

  Baseline (Day 1 of DRI15928) and Week 240

Study Arms (1)

SAR442168

EXPERIMENTAL

SAR442168 : Experimental - Part A: Double-blind period of continued treatment with the respective SAR442168 dose was administered in the DRI15928 study until selection of Phase 3 dose. Part B: Open-label period of a single-group treatment with SAR442168 selected Phase 3 dose of 60 mg. All participants were switched to this 60 mg dose.

Drug: Tolebrutinib

Interventions

Tolebrutinib DRUG

Pharmaceutical form: Film coated tablet Route of administration: Oral

Also known as: SAR442168

SAR442168

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants had to have completed treatment in the DRI15928 study
• The participant had to have given written informed consent prior to undertaking any study related procedure.

You may not qualify if:

• The participant had a confirmed concomitant laboratory or ECG abnormality or medical condition deemed by the investigator incompatible with continuation of SAR442168 treatment.
• The participant had received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) between the last DRI15928 visit and the first treatment visit in the LTS16004 study.
• The participant was receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes.
• The participant was receiving anticoagulant/antiplatelet therapies, including:
• Acetylsalicylic acid (aspirin)
• Antiplatelet drugs (eg, clopidogrel)
• Warfarin (vitamin K antagonist)
• Heparin, including low molecular weight heparin (antithrombin agents)
• Dabigatran (direct thrombin inhibitor)
• Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors)
• Note: All above drugs needed to be stopped at least 5 half-lives before study drug administration except for aspirin, which needed to be stopped at least 8 days beforehand.
• Prior/concurrent clinical study experience. The participant was taking part in another interventional clinical trial of another drug substance.
• Uncooperative behavior or any condition that could make the participant potentially non-adherent with the study procedures
• The participant was pregnant or was a breastfeeding woman.
• The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (37)

North Central Neurology Associates, PC Site Number : 8400005

Cullman, Alabama, 35058, United States

Location

Neurology Associates, PA Site Number : 8400002

Maitland, Florida, 32761, United States

Location

University of South Florida Site Number : 8400009

Tampa, Florida, 33612, United States

Location

Velocity Clinical Research Site Number : 8400007

Savannah, Georgia, 31406, United States

Location

Consultants In Neurology Site Number : 8400001

Northbrook, Illinois, 60062, United States

Location

UC Health, LLC Site Number : 8400008

Dayton, Ohio, 45417, United States

Location

MDH Research LLC Site Number : 8400006

Westerville, Ohio, 43081, United States

Location

Neurology PC Site Number : 8400003

Knoxville, Tennessee, 37922, United States

Location

Investigational Site Number : 1240003

Vancouver, British Columbia, V6T 2B5, Canada

Location

Investigational Site Number : 1240001

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Investigational Site Number : 2030007

Brno, 62500, Czechia

Location

Investigational Site Number : 2030004

Hradec Králové, 50005, Czechia

Location

Investigational Site Number : 2030003

Jihlava, 58633, Czechia

Location

Investigational Site Number : 2030005

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030006

Pardubice, 53203, Czechia

Location

Investigational Site Number : 2030001

Prague, 12808, Czechia

Location

Investigational Site Number : 2030002

Praha 5 - Motol, 15006, Czechia

Location

Investigational Site Number : 2330001

Tallinn, 11315, Estonia

Location

Investigational Site Number : 2500004

Nancy, 54035, France

Location

Investigational Site Number : 5280001

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number : 6430006

Kazan', 420032, Russia

Location

Investigational Site Number : 6430003

Moscow, 125367, Russia

Location

Investigational Site Number : 6430005

Saint Petersburg, 194044, Russia

Location

Investigational Site Number : 6430001

Saint Petersburg, 197110, Russia

Location

Investigational Site Number : 6430007

Tyumen, 625000, Russia

Location

Investigational Site Number : 7240003

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number : 7240002

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240005

Salt, Girona [Gerona], 17190, Spain

Location

Investigational Site Number : 7240001

Madrid, 28007, Spain

Location

Investigational Site Number : 7240004

Murcia, 30120, Spain

Location

Investigational Site Number : 8040002

Chernivtsi, 58000, Ukraine

Location

Investigational Site Number : 8040005

Dnipro, 49038, Ukraine

Location

Investigational Site Number : 8040001

Lviv, 79010, Ukraine

Location

Investigational Site Number : 8040006

Lviv, 79013, Ukraine

Location

Investigational Site Number : 8040009

Odesa, 65025, Ukraine

Location

Investigational Site Number : 8040003

Vinnytsia, 21005, Ukraine

Location

Investigational Site Number : 8040007

Zhytomyr, 10002, Ukraine

Location

Related Links

• LTS16004 Plain Language Results Summary

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 24, 2019
• Study Start: September 23, 2019
• Primary Completion: November 26, 2024
• Study Completion: November 26, 2024
• Last Updated: October 23, 2025
• Results First Posted: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (5); CA (2); NL (1); ES (1); UA (7); FR (1); CZ (7); US (8)