Official Title
A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis
Brief Summary

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

Detailed Description

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.

Active, not recruiting
Secondary Progressive Multiple Sclerosis

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

Eligibility Criteria

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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 60 Years
Countries
Argentina
Australia
Austria
Belarus
Belgium
Bulgaria
Canada
China
Czechia
Denmark
Finland
France
Germany
Greece
Hungary
India
Israel
Italy
Japan
Lithuania
Netherlands
Norway
Poland
Portugal
Romania
Russian Federation
Spain
Turkey
Ukraine
United Kingdom
United States
Locations

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

NCT Number
MeSH Terms
Neoplasm Metastasis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis