Primary Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS Secondary Objective: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS 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 24 to 48 months.
Participants completing the treatment period will be proposed to enroll in a separate long
term safety study.
Drug: Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral
Other Name: SAR442168
Drug: Placebo to match Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral
Inclusion criteria :
- 18 to 60 years of age inclusive
- Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the
2017 McDonald criteria
- Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at
screening
- The participant must have documented evidence of disability progression observed
during the 12 months before screening
- Absence of clinical relapses for at least 24 months
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies
- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP OR
- Is a WOCBP and agrees to use an acceptable contraceptive method
Exclusion criteria:
- The participant has conditions that would adversely affect study participation such as
short life expectancy.
- History of organ transplant.
- Evidence of infection with human immuodeficiency virus (HIV), transplantation,
progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or
latent tuberculosis or other active infections that would adversely affect study
participation.
- Persistent chronic or active or recurring system infection, that may adversely affect
participation or IMP administration in this study, as judged by the Investigator.
- History of malignancy within 5 years prior to screening.
- History of alcohol or drug abuse within 1 year prior to screening.
- Hospitalized for psychiatric disease within 2 years prior to screening.
- Clinically significant laboratory abnormalities (including evidence of liver injury)
or electrocardiogram abnormalities at screening
- Bleeding disorder, known platelet dysfunctionat any time prior to the screening visit
- A platelet count <150 000/μL at the screening visit
- A history of significant bleeding event within 6 months prior to screening, according
to the Investigator's judgment such as, but not limited to cerebral or
gastrointestinal bleeding.
- Lymphocyte count below the lower limit of normal at screening.
- Recent live (attenuated) vaccine within 2 months before the first treatment visit.
- Recent major surgery (within 4 weeks of screening) or planned major surgery during the
study.
- The participant has received medications/treatments for MS within a specified time
frame.
- Receiving potent and moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) or
potent inhibitors of CYP2C8 hepatic enzymes.
- Receiving anticoagulant or antiplatelet therapy (such as aspirin>81mg/day,
clopidogrel, warfarin).
- Contraindications to magnetic resonance imaging (MRI).
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
Center for Neurology and Spine-Site Number:8400089
Phoenix, Arizona, United States
Arcadia Neurology Center-Site Number:8400070
Arcadia, California, United States
UC San Diego ACTRI-Site Number:8400101
La Jolla, California, United States
Collaborative Neuroscience Research-Site Number:8400045
Long Beach, California, United States
Multiple Sclerosis Center-Site Number:8400143
Los Angeles, California, United States
University of San Francisco, Sandler Neurosciences Center-Site Number:8400137
San Francisco, California, United States
Harbor UCLA-Site Number:8400088
Torrance, California, United States
Regina Berkovich, MD, PhD-Site Number:8400059
West Hollywood, California, United States
Mountain Neurological Research Center, Inc.-Site Number:8400128
Basalt, Colorado, United States
University of Colorado-Site Number:8400012
Denver, 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
Neurology Associates, PA-Site Number:8400004
Maitland, Florida, United States
Aqualane Clinical Research-Site Number:8400027
Naples, 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
University of Kansas Medical Center-Site Number:8400023
Kansas City, Kansas, United States
CHI Saint Joseph Medical Group Neurology-Site Number:8400110
Lexington, Kentucky, United States
Tufts Medical Center-Site Number:8400072
Boston, Massachusetts, United States
University of Massachusetts-Site Number:8400014
Worcester, Massachusetts, United States
Wayne State University-Site Number:8400046
Detroit, Michigan, United States
The Memorial Hospital-Site Number:8400033
Owosso, Michigan, United States
Minneapolis Clinic of Neurology-Site Number:8400051
Minneapolis, Minnesota, United States
Mayo Clinic-Site Number:8400111
Rochester, Minnesota, United States
Missouri Baptist Medical Center-Site Number:8400019
Saint Louis, Missouri, United States
Lou Ruvo Center for Brain Health-Site Number:8400117
Las Vegas, Nevada, United States
Holy Name Hospital-Site Number:8400104
Teaneck, New Jersey, United States
University of New Mexico-Site Number:8400032
Albuquerque, New Mexico, United States
Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038
New York, New York, United States
Neurology Associates of Stony Brook-Site Number:8400042
Stony Brook, New York, 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
University Hospitals CMC-Site Number:8400083
Cleveland, Ohio, United States
Cleveland Clinic-Site Number:8400125
Cleveland, Ohio, United States
Optimed Research, LTD-Site Number:8400147
Columbus, Ohio, United States
Neurology Specialists-Site Number:8400002
Dayton, Ohio, United States
Columbus Neuroscience-Site Number:8400010
Westerville, Ohio, United States
Providence Multiple Sclerosis Center-Site Number:8400020
Portland, Oregon, United States
Perelman Center for Advanced Medicine-Site Number:8400142
Philadelphia, Pennsylvania, United States
Jefferson Neurology Associates-Site Number:8400016
Philadelphia, Pennsylvania, United States
Premier Neurology-Site Number:8400069
Greer, South Carolina, United States
Mountain View Clinical Research-Site Number:8400024
Greer, South Carolina, United States
Neurology Clinic, PC-Site Number:8400087
Cordova, Tennessee, United States
Advanced Neuroscience Center-Site Number:8400035
Franklin, Tennessee, United States
Baylor College of Medicine-Site Number:8400136
Houston, Texas, United States
Neurology Center of San Antonio-Site Number:8400036
San Antonio, Texas, United States
University Of Vermont College Of Medicine-Site Number:8400130
Burlington, Vermont, United States
Medical College of Wisconsin-Site Number:8400028
Milwaukee, Wisconsin, United States
Investigational Site Number :0320002
Capital Federal, Buenos Aires, Argentina
Investigational Site Number :0320001
Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number :0320007
Buenos Aires, Argentina
Investigational Site Number :0320006
Córdoba, Argentina
Investigational Site Number :0320005
San Miguel de Tucuman, Argentina
Investigational Site Number :0360003
Woolloongabba, Queensland, Australia
Investigational Site Number :0360002
Kent Town, South Australia, Australia
Investigational Site Number :0360004
Hobart, Tasmania, Australia
Investigational Site Number :0360001
Fitzroy, Victoria, Australia
Investigational Site Number :0360006
Heidelberg West, Victoria, Australia
Investigational Site Number :0400003
Innsbruck, Austria
Investigational Site Number :0400001
Linz, Austria
Investigational Site Number :0400004
Linz, Austria
Investigational Site Number :0400002
Wien, Austria
Investigational Site Number :1120004
Vitebsk, Belarus
Investigational Site Number :1120005
Vitebsk, Belarus
Investigational Site Number :0560007
Bruxelles, Belgium
Investigational Site Number :0560003
Edegem, Belgium
Investigational Site Number :0560006
Leuven, Belgium
Investigational Site Number :0560008
Liège, Belgium
Investigational Site Number :0560002
Mons, Belgium
Investigational Site Number :0560001
Pelt, Belgium
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 :1240017
Burnaby, British Columbia, Canada
Investigational Site Number :1240011
Halifax, Nova Scotia, Canada
Investigational Site Number :1240003
Ottawa, Ontario, Canada
Investigational Site Number :1240008
Toronto, Ontario, Canada
Investigational Site Number :1240006
Gatineau, Quebec, Canada
Investigational Site Number :1240005
Greenfield Park, Quebec, Canada
Investigational Site Number :1240004
Montreal, Quebec, Canada
Investigational Site Number :1240015
Montreal, Quebec, Canada
Investigational Site Number :1240007
Sherbrooke, Quebec, Canada
Investigational Site Number :1240021
Quebec, Canada
Investigational Site Number :1560006
Beijing, China
Investigational Site Number :1560012
Beijing, China
Investigational Site Number :1560021
Beijing, China
Investigational Site Number :1560003
Beijing, China
Investigational Site Number :1560009
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 :1560001
Guangzhou, China
Investigational Site Number :1560007
Hangzhou, China
Investigational Site Number :1560014
Shijiazhuang, China
Investigational Site Number :1560008
Taiyuan, China
Investigational Site Number :1560017
Xi'an, China
Investigational Site Number :2030002
Brno, Czechia
Investigational Site Number :2030004
Hradec Kralove, Czechia
Investigational Site Number :2030001
Jihlava, Czechia
Investigational Site Number :2030010
Ostrava - Poruba, Czechia
Investigational Site Number :2030005
Praha 2, Czechia
Investigational Site Number :2030003
Teplice, Czechia
Investigational Site Number :2080001
Esbjerg, Denmark
Investigational Site Number :2080005
Holstebro, Denmark
Investigational Site Number :2080004
Odense, Denmark
Investigational Site Number :2460003
Helsinki, Finland
Investigational Site Number :2460001
Tampere, Finland
Investigational Site Number :2460002
Turku, Finland
Investigational Site Number :2500011
Bron, France
Investigational Site Number :2500005
Clermont Ferrand, France
Investigational Site Number :2500015
Gonesse, France
Investigational Site Number :2500009
Lille, France
Investigational Site Number :2500006
Montpellier, France
Investigational Site Number :2500008
Nancy, France
Investigational Site Number :2500010
Nantes, France
Investigational Site Number :2500017
Nimes, France
Investigational Site Number :2500016
Paris, France
Investigational Site Number :2500014
Paris, France
Investigational Site Number :2500007
Paris, France
Investigational Site Number :2500003
Rennes, France
Investigational Site Number :2500001
Strasbourg, France
Investigational Site Number :2500012
Toulouse, France
Investigational Site Number :2760005
Bayreuth, Germany
Investigational Site Number :2760009
Berlin, Germany
Investigational Site Number :2760001
Dresden, Germany
Investigational Site Number :2760012
Essen, Germany
Investigational Site Number :2760002
Gießen, Germany
Investigational Site Number :2760010
Halle (Saale), Germany
Investigational Site Number :2760006
Hannover, Germany
Investigational Site Number :2760008
Münster, Germany
Investigational Site Number :2760004
Rostock, Germany
Investigational Site Number :2760011
Ulm, 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 :3000004
Larissa, Greece
Investigational Site Number :3000003
Thessaloniki, Greece
Investigational Site Number :3000005
Thessaloniki, Greece
Investigational Site Number :3480008
Budapest, Hungary
Investigational Site Number :3480004
Budapest, Hungary
Investigational Site Number :3480007
Budapest, Hungary
Investigational Site Number :3480002
Pécs, Hungary
Investigational Site Number :3480001
Szeged, Hungary
Investigational Site Number :3480006
Tatabánya, Hungary
Investigational Site Number :3560007
Gurgaon, India
Investigational Site Number :3560003
Gurgaon, India
Investigational Site Number :3560005
India, India
Investigational Site Number :3560004
Mangaluru, India
Investigational Site Number :3560006
New Delhi, India
Investigational Site Number :3560002
New Delhi, India
Investigational Site Number :3760002
Ashkelon, Israel
Investigational Site Number :3760003
Haifa, Israel
Investigational Site Number :3760008
Jerusalem, Israel
Investigational Site Number :3760001
Tel HaShomer, Israel
Investigational Site Number :3760004
Zefat, Israel
Investigational Site Number :3800011
Bergamo, Italy
Investigational Site Number :3800007
Cagliari, Italy
Investigational Site Number :3800012
Firenze, Italy
Investigational Site Number :3800016
Firenze, Italy
Investigational Site Number :3800014
Genova, Italy
Investigational Site Number :3800013
L'Aquila, Italy
Investigational Site Number :3800004
Milano, Italy
Investigational Site Number :3800001
Milano, Italy
Investigational Site Number :3800010
Milano, Italy
Investigational Site Number :3800008
Pavia, Italy
Investigational Site Number :3800005
Roma, Italy
Investigational Site Number :3800009
Roma, Italy
Investigational Site Number :3920016
Chiba-shi, Chiba, Japan
Investigational Site Number :3920022
Morioka-shi, Iwate, Japan
Investigational Site Number :3920011
Kyoto-shi, Kyoto, Japan
Investigational Site Number :3920020
Sendai-shi, Miyagi, 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 :3920003
Kodaira-shi, Tokyo, Japan
Investigational Site Number :3920010
Ota-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 :4400001
Vilnius, Lithuania
Investigational Site Number :5280001
Amsterdam, Netherlands
Investigational Site Number :5280003
Breda, Netherlands
Investigational Site Number :5280006
Groningen, Netherlands
Investigational Site Number :5280002
Sittard-Geleen, Netherlands
Investigational Site Number :5780003
Bergen, Norway
Investigational Site Number :5780002
Namsos, Norway
Investigational Site Number :5780001
Oslo, Norway
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 :6160002
Katowice, Slaskie, Poland
Investigational Site Number :6160007
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 :6160012
Lublin, Poland
Investigational Site Number :6160011
Zabrze, Poland
Investigational Site Number :6200001
Braga, Portugal
Investigational Site Number :6200011
Lisboa, Portugal
Investigational Site Number :6200007
Lisboa, Portugal
Investigational Site Number :6200006
Lisboa, Portugal
Investigational Site Number :6200002
Matosinhos, Portugal
Investigational Site Number :6200010
Porto, Portugal
Investigational Site Number :6420008
Bucuresti, Romania
Investigational Site Number :6420004
Campulung, Romania
Investigational Site Number :6420006
Cluj-Napoca, Romania
Investigational Site Number :6420003
Constanta, Romania
Investigational Site Number :6420013
Oradea, Romania
Investigational Site Number :6420005
Sibiu, Romania
Investigational Site Number :6420001
Targu Mures, Romania
Investigational Site Number :6420002
Timisoara, Romania
Investigational Site Number :6430018
Barnaul, Russian Federation
Investigational Site Number :6430023
Ekaterinburg, Russian Federation
Investigational Site Number :6430025
Kaliningrad, Russian Federation
Investigational Site Number :6430003
Kazan, Russian Federation
Investigational Site Number :6430022
Kemerovo, Russian Federation
Investigational Site Number :6430017
Kirov, Russian Federation
Investigational Site Number :6430024
Krasnoyarsk, Russian Federation
Investigational Site Number :6430020
Moscow, Russian Federation
Investigational Site Number :6430002
Moscow, Russian Federation
Investigational Site Number :6430013
Moscow, Russian Federation
Investigational Site Number :6430001
Moscow, Russian Federation
Investigational Site Number :6430008
Moscow, Russian Federation
Investigational Site Number :6430021
Nizhny Novgorod, Russian Federation
Investigational Site Number :6430006
Nizhny Novgorod, Russian Federation
Investigational Site Number :6430005
Novosibirsk, Russian Federation
Investigational Site Number :6430026
Perm, Russian Federation
Investigational Site Number :6430007
Pyatigorsk, Russian Federation
Investigational Site Number :6430016
Rostov-on-Don, Russian Federation
Investigational Site Number :6430004
Saint-Petersburg, Russian Federation
Investigational Site Number :6430009
Samara, Russian Federation
Investigational Site Number :6430019
Saransk, Russian Federation
Investigational Site Number :6430014
Smolensk, Russian Federation
Investigational Site Number :6430011
St-Petersburg, Russian Federation
Investigational Site Number :6430012
Tyumen, Russian Federation
Investigational Site Number :6430010
Ufa, Russian Federation
Investigational Site Number :7240007
Sevilla, Andalucia, Spain
Investigational Site Number :7240013
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240016
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240014
Salt, Girona [Gerona], Spain
Investigational Site Number :7240017
Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number :7240004
Majadahonda, Madrid, Spain
Investigational Site Number :7240001
Pozuelo De Alarcón, Madrid, Spain
Investigational Site Number :7240012
Donostia, Pais Vasco, Spain
Investigational Site Number :7240008
Córdoba, Spain
Investigational Site Number :7240015
Lleida, Spain
Investigational Site Number :7240005
Madrid, Spain
Investigational Site Number :7240002
Madrid, Spain
Investigational Site Number :7240003
Madrid, Spain
Investigational Site Number :7240010
Murcia, Spain
Investigational Site Number :7240009
Málaga, Spain
Investigational Site Number :7240011
Valencia, Spain
Investigational Site Number :7920005
Eskisehir, Turkey
Investigational Site Number :7920010
Hatay, Turkey
Investigational Site Number :7920002
Istanbul, Turkey
Investigational Site Number :7920009
Istanbul, Turkey
Investigational Site Number :7920007
Istanbul, Turkey
Investigational Site Number :7920006
Istanbul, Turkey
Investigational Site Number :7920003
Istanbul, Turkey
Investigational Site Number :7920013
Izmir, Turkey
Investigational Site Number :7920001
Izmit, Turkey
Investigational Site Number :7920011
Kütahya, Turkey
Investigational Site Number :7920012
Mersin, Turkey
Investigational Site Number :7920008
Trabzon, Turkey
Investigational Site Number :8040008
Chernivtsi, Ukraine
Investigational Site Number :8040016
Chernivtsi, Ukraine
Investigational Site Number :8040003
Dnipro, Ukraine
Investigational Site Number :8040010
Ivano-Frankivsk, Ukraine
Investigational Site Number :8040007
Kharkiv, Ukraine
Investigational Site Number :8040011
Kharkiv, Ukraine
Investigational Site Number :8040012
Kharkiv, Ukraine
Investigational Site Number :8040013
Kyiv, Ukraine
Investigational Site Number :8040005
Lutsk, Ukraine
Investigational Site Number :8040009
Lviv, Ukraine
Investigational Site Number :8040004
Lviv, Ukraine
Investigational Site Number :8040002
Odesa, Ukraine
Investigational Site Number :8040006
Vinnytsia, Ukraine
Investigational Site Number :8040014
Zhytomyr, Ukraine
Investigational Site Number :8260003
Exeter, Devon, United Kingdom
Investigational Site Number :8260008
Plymouth, Devon, United Kingdom
Investigational Site Number :8260010
Swansea, Neath Port Talbot, United Kingdom
Investigational Site Number :8260012
Nottingham, Nottinghamshire, United Kingdom
Investigational Site Number :8260013
Oxford, Oxfordshire, United Kingdom
Investigational Site Number :8260009
Bristol, United Kingdom
Investigational Site Number :8260001
Cardiff, United Kingdom
Investigational Site Number :8260005
London, United Kingdom
Investigational Site Number :8260018
London, United Kingdom
Investigational Site Number :8260014
Newcastle Upon Tyne, United Kingdom
Investigational Site Number :8260019
Salford, United Kingdom
Clinical Sciences & Operations, Study Director
Sanofi