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 population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety 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)
- 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 multiple sclerosis (PPMS)
according to the 2017 revision of the McDonald diagnostic criteria or with
nonrelapsing secondary progressive multiple sclerosis (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.
University of Alabama MS Center-Site Number:8400013
Birmingham, Alabama, United States
University of San Francisco, Sandler Neurosciences Center-Site Number:8400137
San Francisco, California, United States
University of Colorado-Site Number:8400012
Aurora, Colorado, United States
Georgetown University Medical Center-Site Number:8400119
Washington, District of Columbia, United States
Beth Israel Deaconess Medical Center-Site Number:8400064
Fort Myers, Florida, United States
Axiom Clinical Research of Florida-Site Number:8400001
Tampa, 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
Tufts Medical Center-Site Number:8400072
Boston, Massachusetts, United States
Michigan Institute For Neurological Disorders-Site Number:8400058
Farmington Hills, Michigan, United States
The Memorial Hospital-Site Number:8400033
Owosso, Michigan, United States
Sharlin Health & Neurology-Site Number:8400093
Ozark, Missouri, United States
Missouri Baptist Medical Center-Site Number:8400019
Saint Louis, Missouri, United States
Meridian Clinical Research, LLC-Site Number:8400005
Raleigh, North Carolina, United States
Wake Forest University Baptist Medical Center-Site Number:8400116
Winston-Salem, North Carolina, United States
The Ohio State University Wexner Medical Center-Site Number:8400150
Columbus, Ohio, United States
Optimed Research, LTD-Site Number:8400147
Columbus, Ohio, United States
Columbus Neuroscience-Site Number:8400010
Westerville, Ohio, United States
Oklahoma Medical Research Foundation-Site Number:8400018
Oklahoma City, Oklahoma, United States
Providence Multiple Sclerosis Center-Site Number:8400020
Portland, Oregon, United States
University of Texas Southwestern Medical Center-Site Number:8400077
Dallas, Texas, United States
Multiple Sclerosis Center, Swedish Neuroscience Institute-Site Number:8400121
Seattle, Washington, United States
Investigational Site Number :0400004
Linz, Austria
Investigational Site Number :1120005
Vitebsk, Belarus
Investigational Site Number :1120004
Vitebsk, Belarus
Investigational Site Number :1000002
Pleven, Bulgaria
Investigational Site Number :1000005
Plovdiv, Bulgaria
Investigational Site Number :1000004
Sofia, Bulgaria
Investigational Site Number :1000008
Sofia, Bulgaria
Investigational Site Number :1000001
Sofia, Bulgaria
Investigational Site Number :1000006
Sofia, Bulgaria
Investigational Site Number :1000009
Sofia, Bulgaria
Investigational Site Number :1240016
Vancouver, British Columbia, Canada
Investigational Site Number :1240003
Ottawa, Ontario, Canada
Investigational Site Number :1240013
Toronto, Ontario, Canada
Investigational Site Number :1240006
Gatineau, Quebec, Canada
Investigational Site Number :1560022
Baotou, China
Investigational Site Number :1560006
Beijing, China
Investigational Site Number :1560010
Beijing, China
Investigational Site Number :1560012
Beijing, China
Investigational Site Number :1560023
Beijing, China
Investigational Site Number :1560001
Beijing, China
Investigational Site Number :1560009
Beijing, China
Investigational Site Number :1560025
Beijing, China
Investigational Site Number :1560021
Beijing, China
Investigational Site Number :1560004
Changchun, China
Investigational Site Number :1560015
Changsha, China
Investigational Site Number :1560005
Chengdu, China
Investigational Site Number :1560019
Chongqing, China
Investigational Site Number :1560035
Fuzhou, China
Investigational Site Number :1560016
Guangzhou, China
Investigational Site Number :1560028
Guangzhou, China
Investigational Site Number :1560002
Guangzhou, China
Investigational Site Number :1560027
Hohhot, China
Investigational Site Number :1560044
Nanjing, China
Investigational Site Number :1560042
Nanjing, China
Investigational Site Number :1560003
Shanghai, China
Investigational Site Number :1560018
Shenyang, China
Investigational Site Number :1560014
Shijiazhuang, China
Investigational Site Number :1560008
Taiyuan, China
Investigational Site Number :1560020
Tianjin, China
Investigational Site Number :1560011
Wuhan, China
Investigational Site Number :1560017
Xi'an, China
Investigational Site Number :1560033
Yinchuan, China
Investigational Site Number :2030004
Hradec Kralove, Czechia
Investigational Site Number :2030009
Pardubice, Czechia
Investigational Site Number :2030003
Teplice, Czechia
Investigational Site Number :2030007
Zlin, Czechia
Investigational Site Number :2080001
Esbjerg, Denmark
Investigational Site Number :2080005
Holstebro, Denmark
Investigational Site Number :2330001
Tallinn, Estonia
Investigational Site Number :2330002
Tartu, Estonia
Investigational Site Number :2460003
Helsinki, Finland
Investigational Site Number :2460001
Tampere, Finland
Investigational Site Number :2460002
Turku, Finland
Investigational Site Number :2760001
Dresden, Germany
Investigational Site Number :2760019
Düsseldorf, Germany
Investigational Site Number :2760016
Hamburg, Germany
Investigational Site Number :2760008
Münster, Germany
Investigational Site Number :2760004
Rostock, Germany
Investigational Site Number :2760011
Ulm, Germany
Investigational Site Number :3800002
Pozzilli, Isernia, Italy
Investigational Site Number :3800007
Orbassano, Torino, Italy
Investigational Site Number :3800011
Bergamo, Italy
Investigational Site Number :3800015
Catania, Italy
Investigational Site Number :3800012
Firenze, Italy
Investigational Site Number :3800014
Genova, Italy
Investigational Site Number :3800001
Milano, Italy
Investigational Site Number :3800010
Milano, Italy
Investigational Site Number :3800003
Napoli, Italy
Investigational Site Number :3800006
Napoli, Italy
Investigational Site Number :3800008
Pavia, Italy
Investigational Site Number :3800005
Roma, Italy
Investigational Site Number :3800009
Roma, Italy
Investigational Site Number :3800013
Roma, Italy
Investigational Site Number :3920016
Chiba-shi, Chiba, Japan
Investigational Site Number :3920008
Koriyama-shi, Fukushima, Japan
Investigational Site Number :3920012
Tsukuba-shi, Ibaraki, Japan
Investigational Site Number :3920022
Morioka-shi, Iwate, Japan
Investigational Site Number :3920005
Niigata-shi, Niigata, Japan
Investigational Site Number :3920004
Moriguchi-shi, Osaka, Japan
Investigational Site Number :3920001
Osaka-shi, Osaka, Japan
Investigational Site Number :3920018
Kawagoe-shi, Saitama, Japan
Investigational Site Number :3920014
Bunkyo-ku, Tokyo, Japan
Investigational Site Number :3920003
Kodaira-shi, Tokyo, Japan
Investigational Site Number :3920010
Ota-ku, Tokyo, Japan
Investigational Site Number :3920013
Shinjuku-ku, Tokyo, Japan
Investigational Site Number :3920009
Ube-shi, Yamaguchi, Japan
Investigational Site Number :3920023
Sagamihara-shi, Japan
Investigational Site Number :4400003
Kaunas, Lithuania
Investigational Site Number :4400002
Klaipeda, Lithuania
Investigational Site Number :4400004
Siauliai, Lithuania
Investigational Site Number :4400001
Vilnius, Lithuania
Investigational Site Number :4840002
Mexico, Mexico
Investigational Site Number :4840001
Mexico, Mexico
Investigational Site Number :4840003
Veracruz, Mexico
Investigational Site Number :6160003
Bydgoszcz, Kujawsko-pomorskie, Poland
Investigational Site Number :6160005
Warszawa, Mazowieckie, Poland
Investigational Site Number :6160006
Warszawa, Mazowieckie, Poland
Investigational Site Number :6160009
Glogow Mlp., Podkarpackie, Poland
Investigational Site Number :6160002
Katowice, Slaskie, Poland
Investigational Site Number :6160004
Katowice, Slaskie, Poland
Investigational Site Number :6160008
Plewiska, Wielkopolskie, Poland
Investigational Site Number :6160001
Lodz, Poland
Investigational Site Number :6420015
Brasov, Romania
Investigational Site Number :6420008
Bucuresti, Romania
Investigational Site Number :6420004
Campulung, Romania
Investigational Site Number :6420003
Constanta, Romania
Investigational Site Number :6420010
Oradea, Romania
Investigational Site Number :6420005
Sibiu, Romania
Investigational Site Number :6420001
Targu Mures, Romania
Investigational Site Number :6420002
Timisoara, Romania
Investigational Site Number :6430014
Krasnoyarsk, Russian Federation
Investigational Site Number :6430002
Moscow, Russian Federation
Investigational Site Number :6430008
Moscow, Russian Federation
Investigational Site Number :6430011
Nizhny Novgorod, Russian Federation
Investigational Site Number :6430003
Nizhny Novgorod, Russian Federation
Investigational Site Number :6430007
Pyatigorsk, Russian Federation
Investigational Site Number :6430012
Rostov-on-Don, Russian Federation
Investigational Site Number :6430005
Samara, Russian Federation
Investigational Site Number :6430009
Smolensk, Russian Federation
Investigational Site Number :6430001
St-Petersburg, Russian Federation
Investigational Site Number :6430006
Tyumen, Russian Federation
Investigational Site Number :6430004
Ufa, Russian Federation
Investigational Site Number :7240003
Sevilla, Andalucia, Spain
Investigational Site Number :7240009
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240001
Pozuelo De Alarcón, Madrid, Spain
Investigational Site Number :7240008
Donostia, Pais Vasco, Spain
Investigational Site Number :7240004
Córdoba, Spain
Investigational Site Number :7240006
Murcia, Spain
Investigational Site Number :7240005
Málaga, Spain
Investigational Site Number :7240007
Valencia, Spain
Investigational Site Number :7520001
Göteborg, Sweden
Investigational Site Number :7520002
Stockholm, Sweden
Investigational Site Number :1580007
Hsinchu City, Taiwan
Investigational Site Number :1580005
Kaohsiung, Taiwan
Investigational Site Number :1580003
Taichung, Taiwan
Investigational Site Number :1580002
Taipei, Taiwan
Investigational Site Number :1580006
Taoyuang, Taiwan
Investigational Site Number :7920005
Eskisehir, Turkey
Investigational Site Number :7920011
Hatay, Turkey
Investigational Site Number :7920002
Istanbul, Turkey
Investigational Site Number :7920009
Istanbul, Turkey
Investigational Site Number :7920007
Istanbul, Turkey
Investigational Site Number :7920003
Istanbul, Turkey
Investigational Site Number :7920008
Izmir, Turkey
Investigational Site Number :7920010
Izmir, Turkey
Investigational Site Number :7920001
Kocaeli, Turkey
Investigational Site Number :7920006
Mersin, Turkey
Investigational Site Number :8040011
Ivano-Frankivsk, Ukraine
Investigational Site Number :8040016
Kharkiv, Ukraine
Investigational Site Number :8040013
Kharkiv, Ukraine
Investigational Site Number :8040008
Kherson, Ukraine
Investigational Site Number :8040014
Kyiv, Ukraine
Investigational Site Number :8040010
Lutsk, Ukraine
Investigational Site Number :8040001
Lviv, Ukraine
Investigational Site Number :8040009
Odesa, Ukraine
Clinical Sciences & Operations, Study Director
Sanofi