Tolebrutinib: Pharmaceutical form:Tablet-Route of administration:oral
Placebo: Pharmaceutical form:Tablet-Route of administration:oral
Teriflunomide: Pharmaceutical form:Tablet-Route of administration:oral
Study summary
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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
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 — From baseline until the End of study approximately 4 years per participant
Number of Participants with Potentially clinically significant abnormalities (PCSAs) — From baseline until the End of study approximately 4 years per participant Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs and safety findings on MRI during the study period.
Trial sites (352)
Facility
City
Region
Status
The University of Alabama at Birmingham- Site Number : 8400013
Birmingham
Alabama
~North Central Neurology Associates, PC- Site Number : 8400009
Cullman
Alabama
Center for Neurology and Spine- Site Number : 8400089
Phoenix
Arizona
Collaborative Neuroscience Research- Site Number : 8400045
Los Alamitos
California
USC- Site Number : 8400143
Los Angeles
California
University of California San Diego Medical Center- Site Number : 8400101
San Diego
California
Regina Berkovich, MD, PhD- Site Number : 8400059
West Hollywood
California
University of Colorado- Site Number : 8400012
Denver
Colorado
Advanced Neurosciences Research- Site Number : 8400025
Fort Collins
Colorado
Georgetown University Medical Center- Site Number : 8400119
Washington D.C.
District of Columbia
SFM Clinical Research, LLC- Site Number : 8400029
Boca Raton
Florida
University of Florida Health- Site Number : 8400159
Gainesville
Florida
Neurology Associates- Site Number : 8409902
Maitland
Florida
University of Miami- Site Number : 8400063
Miami
Florida
Aqualane Clinical Research- Site Number : 8400027
Naples
Florida
Axiom Clinical Research of Florida- Site Number : 8400001
Tampa
Florida
University of South Florida- Site Number : 8409905
Tampa
Florida
Velocity Clinical Research- Site Number : 8409903
Savannah
Georgia
Consultants In Neurology- Site Number : 8409906
Northbrook
Illinois
Springfield Clinic, LLP- Site Number : 8400071
Springfield
Illinois
Indiana University Health, Inc- Site Number : 8400039
Fort Wayne
Indiana
University of Kansas Medical Center- Site Number : 8400023
Kansas City
Kansas
University of Kentucky- Site Number : 8400106
Lexington
Kentucky
Norton Neurology MS Services- Site Number : 8400127
Louisville
Kentucky
The NeuroMedical Center- Site Number : 8400057
Baton Rouge
Louisiana
Ochsner Clinic Foundation- Site Number : 8400107
New Orleans
Louisiana
Tufts Medical Center- Site Number : 8400072
Boston
Massachusetts
University of Massachusetts- Site Number : 8400014
Worcester
Massachusetts
Wayne State University- Site Number : 8400046
Detroit
Michigan
Michigan Institute Neuro Disorders- Site Number : 8400058
Farmington Hills
Michigan
Memorial Healthcare Institute for Neuroscience- Site Number : 8400033
Owosso
Michigan
Minneapolis Clinic of Neurology- Site Number : 8400051
Golden Valley
Minnesota
Mayo Clinic- Site Number : 8400111
Rochester
Minnesota
Sharlin Health & Neurology- Site Number : 8400093
Ozark
Missouri
Missouri Baptist Medical Center- Site Number : 8400019
St Louis
Missouri
Lou Ruvo Center for Brain Health- Site Number : 8400117
Las Vegas
Nevada
University of New Mexico- Site Number : 8400032
Albuquerque
New Mexico
Mount Sinai Medical Center- Site Number : 8400038
New York
New York
NYU Langone South Shore Neurologic Associates- Site Number : 8400100
Patchogue
New York
Neurology Associates of Stony Brook- Site Number : 8400042
Stony Brook
New York
+ 312 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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