Primary Objective: To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS Secondary Objective: To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life To evaluate the safety and tolerability of daily SAR442168 To evaluate pharmacodynamics (PD) of SAR442168
Study duration will vary per participant in this event driven trial with a treatment duration
of approximately 18 to 36 months. Participants completing the study will be offered to
participate in a long term safety study.
Drug: Tolebrutinib
Pharmaceutical form: Tablet
Route of administration: Oral
Other Name: SAR442168
Drug: Teriflunomide HMR1726
Pharmaceutical form: Tablet
Route of administration: Oral
Drug: Placebo to match Tolebrutinib
Pharmaceutical form: Tablet
Route of administration: Oral
Drug: Placebo to match Teriflunomide
Pharmaceutical form: Tablet
Route of administration: Oral
Inclusion criteria :
- The participant must be 18 to 55 years of age, inclusive, at the time of signing the
informed consent
- The participant must have been diagnosed with RMS according to the 2017 revision of
the McDonald diagnostic criteria
- The participant has an expanded disability status scale (EDSS) score ≤5.5 at the first
Screening Visit
- The participant must have at least 1 of the following prior to screening:
- ≥1 documented relapse within the previous year OR
- ≥2 documented relapses within the previous 2 years, OR
- ≥1 documented Gd enhancing lesion on an MRI scan within the previous year
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies
- Male participants are eligible to participate if they agree to the following during
the intervention period and until accelerated elimination procedure:
- Refrain from donating sperm
Plus either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent OR
- Must agree to use contraception/barrier as detailed below
- Agree to use a male condom and should also be advised of the benefit for a female
partner to use a highly effective method of contraception as a condom may break or
leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who
is not currently pregnant
- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions apply:
- Is not a WOCBP OR
- Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a
failure rate of <1% per year), preferably with low user dependency during the
intervention period and until accelerated elimination procedure is completed (or for
at least 10 days after the last dose of SAR442168, if the case was unblinded) and
agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the
study and for the same period of time.
- A WOCBP must have a negative highly sensitive pregnancy test at screening and
within 24hours before the first dose of study intervention.
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be excluded
from participation if the serum pregnancy result is positive.
- The Investigator is responsible for review of medical history, menstrual history,
and recent sexual activity to decrease the risk for inclusion of a woman with an
early undetected pregnancy.
- The participant must have given written informed consent prior to undertaking any
study related procedure. This includes consent to comply with the requirements
and restrictions listed in the informed consent form (ICF) and in this protocol.
In countries where the legal age of maturity is greater than 18 years, a specific
ICF for such legally minor participants must also be signed by the participant's
legally authorized representative
Exclusion criteria:
- The participant has been diagnosed with primary progressive multiplesclerosis (PPMS)
according to the 2017 revision of the McDonald diagnostic criteria or with
nonrelapsing secondary progressive multiplesclerosis (SPMS)
- The participant has a history of infection or may be at risk for infection including
but not limited to: HIV, transplantation, live attenuated vaccines, progressive
multifocal leukoencephalopathy, tuberculosis, hepatitis B or C, any persistent chronic
or active recurring infection
- Clinically significant laboratory abnormalities (including evidence of liver injury)
or electrocardiogram abnormalities at Screening.
- The participant has conditions or situations that would adversely affect participation
in this study, including but not limited to:
- A short life expectancy due to pre-existing health condition(s) as determined by
their treating neurologist
- Medical condition(s) or concomitant disease(s) making them nonevaluable for the
primary efficacy endpoint or that would adversely affect participation in this
study, as judged by the Investigator
- A requirement for concomitant treatment that could bias the primary evaluation
- The participant has a history of or currently has concomitant medical or clinical
conditions that would adversely affect participation in this study
- At screening, the participant is positive for hepatitis B surface antigen and/or
hepatitis B core antibody and/or is positive for hepatitis C antibody
- The participant has any of the following:
- A bleeding disorder or known platelet dysfunction at any time prior to the
screening visit
- A platelet count <150 000/μL at the screening visit
- The participant has a lymphocyte count below the lower limit of normal (LLN) at the
screening visit
- The presence of psychiatric disturbance or substance abuse
- Prior/concomitant therapy
- The participant is receiving potent and moderate inducers of cytochrome P450 (CYP) 3A
or potent inhibitors of CYP2C8 hepatic enzymes
- The participant is receiving anticoagulant/antiplatelet therapies
- The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial
North Central Neurology Associates, PC-Site Number:8400009
Cullman, Alabama, United States
Center for Neurology and Spine-Site Number:8400089
Phoenix, Arizona, United States
Arcadia Neurology Center-Site Number:8400070
Arcadia, California, United States
Multiple Sclerosis Center of California-Site Number:8400135
Newport Beach, California, United States
Harbor UCLA-Site Number:8400088
Torrance, California, United States
Mountain Neurological Research Center, Inc.-Site Number:8400128
Basalt, Colorado, United States
Advanced Neurosciences Research-Site Number:8400025
Fort Collins, Colorado, United States
South Florida Neurology Associates-Site Number:8400029
Boca Raton, Florida, United States
University of Florida Health-Site Number:8400159
Gainesville, Florida, United States
Neurology Associates, PA-Site Number:8400004
Maitland, Florida, United States
University of Miami-Site Number:8400063
Miami, Florida, United States
Infinity Clinical Research-Site Number:8400008
Sunrise, Florida, United States
University of South Florida-Site Number:8400006
Tampa, Florida, United States
Meridian Clinical Research-Site Number:8400003
Savannah, Georgia, United States
Consultants In Neurology-Site Number:8400011
Northbrook, Illinois, United States
Prairie Education and Research Cooperative-Site Number:8400071
Springfield, Illinois, United States
Fort Wayne Neurological Center-Site Number:8400039
Fort Wayne, Indiana, United States
CHI Saint Joseph Medical Group Neurology-Site Number:8400110
Lexington, Kentucky, United States
University of Kentucky-Site Number:8400106
Lexington, Kentucky, United States
Norton Neurology MS Services-Site Number:8400127
Louisville, Kentucky, United States
The NeuroMedical Center-Site Number:8400057
Baton Rouge, Louisiana, United States
International Neurorehabilitation Institute-Site Number:8400034
Lutherville-Timonium, Maryland, United States
Wayne State University-Site Number:8400046
Detroit, Michigan, United States
Minneapolis Clinic of Neurology-Site Number:8400051
Minneapolis, Minnesota, United States
Saint Luke's Hospital-Site Number:8400153
Kansas City, Missouri, United States
West Omaha Family Physicians-Site Number:8400139
Omaha, Nebraska, United States
University Of Nebraska-Site Number:8400129
Omaha, Nebraska, United States
Hackensack University Hospital-Site Number:8400047
Hackensack, New Jersey, United States
University of New Mexico-Site Number:8400032
Albuquerque, New Mexico, United States
South Shore Neurologic Associates-Site Number:8400100
Patchogue, New York, United States
Novant Health Multiple Sclerosis Care Center - South Park-Site Number:8400120
Charlotte, North Carolina, United States
Meridian Clinical Research, LLC-Site Number:8400005
Raleigh, North Carolina, United States
Sanford Brain & Spine Center-Site Number:8400126
Fargo, North Dakota, United States
Dayton Center for Neurological Disorders-Site Number:8400081
Centerville, Ohio, United States
Jefferson Neurology Associates-Site Number:8400016
Philadelphia, Pennsylvania, United States
Premier Neurology-Site Number:8400069
Greer, South Carolina, United States
Advanced Neuroscience Center-Site Number:8400035
Franklin, Tennessee, United States
Sibyl Wray, MD, Neurology, PC-Site Number:8400007
Knoxville, Tennessee, United States
Mt Olympus Medical Research-Site Number:8400163
Katy, Texas, United States
Neurology Center of San Antonio-Site Number:8400036
San Antonio, Texas, United States
Texas Institute for Neuroogical Disorders-Sherman-Site Number:8400151
Sherman, Texas, United States
Neurological Associates-Site Number:8400097
Richmond, Virginia, United States
Wheaton Franciscan Healthcare-Site Number:8400022
Milwaukee, Wisconsin, United States
Investigational Site Number :0320004
Caba, Buenos Aires, Argentina
Investigational Site Number :0320002
Capital Federal, Buenos Aires, Argentina
Investigational Site Number :0320001
Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number :0320003
Rosario, Santa Fe, Argentina
Investigational Site Number :0320005
San Miguel de Tucuman, Argentina
Investigational Site Number :0560005
Brugge, Belgium
Investigational Site Number :0560004
Gent, Belgium
Investigational Site Number :0560002
Mons, Belgium
Investigational Site Number :0560001
Pelt, Belgium
Investigational Site Number :0760001
Porto Alegre, Rio Grande Do Sul, Brazil
Investigational Site Number :0760002
Curitiba, Brazil
Investigational Site Number :0760007
Sao Paulo, Brazil
Investigational Site Number :1240002
Edmonton, Alberta, Canada
Investigational Site Number :1240014
London, Ontario, Canada
Investigational Site Number :1240005
Greenfield Park, Quebec, Canada
Investigational Site Number :1240006
Gatineau, Canada
Investigational Site Number :1240021
Quebec, Canada
Investigational Site Number :1520002
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520005
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520001
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520003
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520006
Concepción, Chile
Investigational Site Number :1520004
Valdivia, Chile
Investigational Site Number :1910001
Zagreb, Croatia
Investigational Site Number :1910002
Zagreb, Croatia
Investigational Site Number :1910003
Zagreb, Croatia
Investigational Site Number :2030002
Brno, Czechia
Investigational Site Number :2030011
Hradec Kralove, Czechia
Investigational Site Number :2030001
Jihlava, Czechia
Investigational Site Number :2030008
Praha 10, Czechia
Investigational Site Number :2030005
Praha 5 - Motol, Czechia
Investigational Site Number :2500019
Besancon, France
Investigational Site Number :2500018
Bordeaux, France
Investigational Site Number :2500011
Bron, France
Investigational Site Number :2500005
Clermont Ferrand, France
Investigational Site Number :2500006
Montpellier, France
Investigational Site Number :2500010
Nantes, France
Investigational Site Number :2500002
Nice, France
Investigational Site Number :2500017
Nimes, France
Investigational Site Number :2500007
Paris, France
Investigational Site Number :2500004
Poissy, France
Investigational Site Number :2500003
Rennes, France
Investigational Site Number :2500001
Strasbourg, France
Investigational Site Number :2760005
Bayreuth, Germany
Investigational Site Number :2760015
Berlin, Germany
Investigational Site Number :2760014
Berlin, Germany
Investigational Site Number :2760020
Bochum, Germany
Investigational Site Number :2760012
Essen, Germany
Investigational Site Number :2760003
Würzburg, Germany
Investigational Site Number :3000001
Athens, Greece
Investigational Site Number :3000006
Athens, Greece
Investigational Site Number :3000002
Athens, Greece
Investigational Site Number :3000007
Athens, Greece
Investigational Site Number :3000009
Athens, Greece
Investigational Site Number :3000004
Larissa, Greece
Investigational Site Number :3000003
Thessaloniki, Greece
Investigational Site Number :3480105
Budapest, Hungary
Investigational Site Number :3480102
Budapest, Hungary
Investigational Site Number :3480106
Kaposvár, Hungary
Investigational Site Number :3480103
Tatabánya, Hungary
Investigational Site Number :3560005
Chandigarh, India
Investigational Site Number :3560007
Gurgaon, India
Investigational Site Number :3560008
Gurgaon, India
Investigational Site Number :3560002
New Delhi, India
Investigational Site Number :3560004
Thiruvananthapuram, India
Investigational Site Number :3760002
Ashkelon, Israel
Investigational Site Number :3760003
Haifa, Israel
Investigational Site Number :3760006
Rehovot, Israel
Investigational Site Number :3760004
Safed, Israel
Investigational Site Number :3760001
Tel HaShomer, Israel
Investigational Site Number :4100001
Goyang-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number :4100003
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100006
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100002
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4280002
Riga, Latvia
Investigational Site Number :4280003
Riga, Latvia
Investigational Site Number :5280001
Amsterdam, Netherlands
Investigational Site Number :5780002
Namsos, Norway
Investigational Site Number :5780001
Oslo, Norway
Investigational Site Number :6200001
Braga, Portugal
Investigational Site Number :6200005
Coimbra, Portugal
Investigational Site Number :6200011
Lisboa, Portugal
Investigational Site Number :6200006
Lisboa, Portugal
Investigational Site Number :6200002
Matosinhos, Portugal
Investigational Site Number :6200010
Porto, Portugal
Investigational Site Number :6200004
Santa Maria da Feira, Portugal
San Juan MS Center-Site Number:8400015
Guaynabo, Puerto Rico
Investigational Site Number :6430006
Barnaul, Russian Federation
Investigational Site Number :6430013
Bryansk, Russian Federation
Investigational Site Number :6430012
Ekaterinburg, Russian Federation
Investigational Site Number :6430001
Kazan, Russian Federation
Investigational Site Number :6430010
Kirov, Russian Federation
Investigational Site Number :6430007
Moscow, Russian Federation
Investigational Site Number :6430005
Moscow, Russian Federation
Investigational Site Number :6430003
Novosibirsk, Russian Federation
Investigational Site Number :6430014
Saint-Petersburg, Russian Federation
Investigational Site Number :6430002
Saint-Petersburg, Russian Federation
Investigational Site Number :6430011
Saransk, Russian Federation
Investigational Site Number :6430004
St-Petersburg, Russian Federation
Investigational Site Number :6880001
Belgrade, Serbia
Investigational Site Number :6880003
Belgrade, Serbia
Investigational Site Number :6880006
Belgrade, Serbia
Investigational Site Number :6880002
Kragujevac, Serbia
Investigational Site Number :6880004
Nis, Serbia
Investigational Site Number :6880005
Novi Sad, Serbia
Investigational Site Number :7030001
Bratislava, Slovakia
Investigational Site Number :7030002
Martin, Slovakia
Investigational Site Number :7030004
Nitra, Slovakia
Investigational Site Number :7240011
Sevilla, Andalucia, Spain
Investigational Site Number :7240006
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240009
Barakaldo, Bizkaia, Spain
Investigational Site Number :7240004
Salt, Girona [Gerona], Spain
Investigational Site Number :7240013
Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number :7240007
Hospitalet de Llobregat, Spain
Investigational Site Number :7240008
La Coruña, Spain
Investigational Site Number :7240005
Lleida, Spain
Investigational Site Number :7240003
Madrid, Spain
Investigational Site Number :7240001
Madrid, Spain
Investigational Site Number :7240002
Madrid, Spain
Investigational Site Number :7240010
Málaga, Spain
Investigational Site Number :7240012
Pozuelo De Alarcón, Spain
Investigational Site Number :7560003
Aarau, Switzerland
Investigational Site Number :7560002
Bern, Switzerland
Investigational Site Number :7560004
Lugano, Switzerland
Investigational Site Number :7920002
Ankara, Turkey
Investigational Site Number :7920005
Besevler / Ankara, Turkey
Investigational Site Number :7920006
Istanbul, Turkey
Investigational Site Number :7920004
Kuttahta, Turkey
Investigational Site Number :7920001
Samsun, Turkey
Investigational Site Number :7920003
Trabzon, Turkey
Investigational Site Number :8040020
Chernihiv, Ukraine
Investigational Site Number :8040002
Chernivtsi, Ukraine
Investigational Site Number :8040019
Chernivtsi, Ukraine
Investigational Site Number :8040005
Dnipro, Ukraine
Investigational Site Number :8040022
Kharkiv, Ukraine
Investigational Site Number :8040018
Kharkiv, Ukraine
Investigational Site Number :8040007
Kyiv, Ukraine
Investigational Site Number :8040006
Lviv, Ukraine
Investigational Site Number :8040003
Vinnytsia, Ukraine
Investigational Site Number :8260003
Exeter, Devon, United Kingdom
Investigational Site Number :8260016
Canterbury, Kent, United Kingdom
Investigational Site Number :8260009
Bristol, United Kingdom
Clinical Sciences & Operations, Study Director
Sanofi