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

Long-term Extension Safety and Efficacy Study of SAR442168 in Participants With Relapsing Multiple Sclerosis

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

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Tolebrutinib

Detailed Description

Approximately 62 months including the 8 weeks post-treatment visit

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Investigational Site Number : 1240003
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Investigational Site Number : 1240001
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number : 2030007
  • Hradec Králové, Czechia, 50005
    • Investigational Site Number : 2030004
  • Jihlava, Czechia, 58633
    • Investigational Site Number : 2030003
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number : 2030005
  • Pardubice, Czechia, 53203
    • Investigational Site Number : 2030006
  • Prague, Czechia, 12808
    • Investigational Site Number : 2030001
  • Praha 5 - Motol, Czechia, 15006
    • Investigational Site Number : 2030002
• Estonia
  • Tallinn, Estonia, 11315
    • Investigational Site Number : 2330001
• France
  • Nancy, France, 54035
    • Investigational Site Number : 2500004
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Investigational Site Number : 5280001
• Russia
  • Kazan', Russia, 420032
    • Investigational Site Number : 6430006
  • Moscow, Russia, 125367
    • Investigational Site Number : 6430003
  • Saint Petersburg, Russia, 194044
    • Investigational Site Number : 6430005
  • Saint Petersburg, Russia, 197110
    • Investigational Site Number : 6430001
  • Tyumen, Russia, 625000
    • Investigational Site Number : 6430007
• Spain
  • Madrid, Spain, 28007
    • Investigational Site Number : 7240001
  • Murcia, Spain, 30120
    • Investigational Site Number : 7240004
  • Andalusia
    • Seville, Andalusia, Spain, 41009
      • Investigational Site Number : 7240003
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240002
  • Girona [Gerona]
    • Salt, Girona [Gerona], Spain, 17190
      • Investigational Site Number : 7240005
• Ukraine
  • Chernivtsi, Ukraine, 58000
    • Investigational Site Number : 8040002
  • Dnipro, Ukraine, 49038
    • Investigational Site Number : 8040005
  • Lviv, Ukraine, 79010
    • Investigational Site Number : 8040001
  • Lviv, Ukraine, 79013
    • Investigational Site Number : 8040006
  • Odesa, Ukraine, 65025
    • Investigational Site Number : 8040009
  • Vinnytsia, Ukraine, 21005
    • Investigational Site Number : 8040003
  • Zhytomyr, Ukraine, 10002
    • Investigational Site Number : 8040007
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • North Central Neurology Associates, PC Site Number : 8400005
  • Florida
    • Maitland, Florida, United States, 32761
      • Neurology Associates, PA Site Number : 8400002
    • Tampa, Florida, United States, 33612
      • University of South Florida Site Number : 8400009
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Velocity Clinical Research Site Number : 8400007
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Consultants In Neurology Site Number : 8400001
  • Ohio
    • Dayton, Ohio, United States, 45417
      • UC Health, LLC Site Number : 8400008
    • Westerville, Ohio, United States, 43081
      • MDH Research LLC Site Number : 8400006
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Neurology PC Site Number : 8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Participants had to have completed treatment in the DRI15928 study
• Female participants had to continue to use an acceptable effective contraception method of birth control from inclusion and until the last dose of study drug, except if she had undergone sterilization at least 3 months earlier or was postmenopausal. Menopause was defined as being amenorrheic for ≥12 months with plasma follicle stimulating hormone (FSH) level >30 UI/L.
• The participant had to have given written informed consent prior to undertaking any study related procedure.

Exclusion criteria:

• 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 had received a non-study MS disease modifying treatment between the last IMP treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement of the Investigator may add unjustified risk to switching back and continuing treatment with SAR442168. Washout periods after treatment with non-study DMTs had to be respected except for interferons or glatiramer acetate treatment.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR442168; 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; Pharmaceutical form: Film coated tablet Route of administration: Oral; Other Names: SAR442168

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of New Gadolinium (Gd)-Enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192	Magnetic resonance imaging (MRI) of the brain was performed to identify number of new Gd-enhancing T1-hyperintense lesions. Central review was used to identify new Gd-enhancing T1-hyperintense lesions not present at the previous MRI. mITT=modified intent-to-treat; SAP= statistical analysis plan. Only those participants with data collected at specified timepoints are reported.	Weeks 192 and 240
Mean Number of New or Enlarging T2 Lesions at Week 240 Relative to Week 192	MRI of the brain was performed to identify number of new or enlarging T2 lesions. Central review was used to identify new or enlarging T2 lesions not present at the previous MRI; the values were standardized to per month values by dividing by the number of months (4-week intervals) from the previous MRI to the current MRI.	Weeks 192 and 240
Total Mean Number of Gd-enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192	MRI of the brain was performed to identify number of Gd-enhancing T1-hyperintense lesions. Central review was used to identify Gd-enhancing T1-hyperintense lesions not present at the previous MRI.	Weeks 192 and 240
Annualized Relapse Rate (ARR)	Multiple sclerosis (MS) relapse was defined as acute, new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for >=24 hours with or without recovery, present at normal body temperature and preceded by >=30 days of clinical stability. ARR was the total number of relapses for participants by dose group divided by the sum of the standardized study duration for participants in the dose group.	From Baseline (enrollment in LTS16004, Day 1) to Week 240
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 240	The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal (motor), cerebellar (coordination), sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Baseline assessed for long-term tolebrutinib treatment by change from baseline was defined as the last non-missing value prior to the first administration of randomized study drug in DRI15928 study.	Baseline (Day 1 of DRI15928) and Week 240

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• LTS16004 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): November 26, 2024
• Study Completion (Actual): November 26, 2024

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: LTS16004; 2018-004731-76 (EudraCT Number); U1111-1223-4256 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No