Primary Objective:To determine the efficacy of SAR442168 compared to placebo in delaying disabilityprogression in primary progressive multiple sclerosis (PPMS)Secondary Objectives:To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magneticresonance imaging (MRI) lesions, cognitive performance, physical function, and quality oflife To evaluate safety and tolerability of SAR442168 To evaluate populationpharmacokinetics (PK) of SAR442168 in PPMS and its relationship to efficacy and safety Toevaluate pharmacodynamics of SAR442168
Study duration will vary per participant in this event driven trial with a treatment
duration of approximately 12 to 60 months.
Drug: Tolebrutinib
Pharmaceutical form: Film-coated Tablet Route of administration: Oral
Other Name: SAR442168
Drug: Placebo
Pharmaceutical form: Film-coated Tablet Route of administration: Oral
Inclusion Criteria:
- 18 to 55 years of age inclusive
- Diagnosis of PPMS according to the 2017 McDonald criteria
- Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at
screening inclusive
- Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G
(IgG) index either during screening or documented previous history.
- Contraceptive use consistent with local regulations for individuals participating in
clinical studies
- Participant is eligible to participate if she is not pregnant or breastfeeding, and
at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP) or is a WOCBP and agrees to use an
acceptable contraceptive method
- the participant must not have access to ocrelizumab (eg, ocrelizumab not available
on the national market or not reimbursed for the approved indication).
- the participant must have access to and be eligible to be treated with ocrelizumab
but: 1) does not tolerate it due to side effects or safety reasons; and/or 2) has
failed ocrelizumab treatment due to perceived lack of efficacy
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Participant has conditions that would adversely affect study participation such as
short life expectancy.
- Evidence of infection with human immunodeficiency virus (HIV), transplantation,
progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or
latent tuberculosis or other active infection 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.
- 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.
- 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
- 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 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).
NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended
to contain all considerations relevant to a patient's potential participation in a
clinical trial
UC San Diego ACTRI Site Number : 8400101
La Jolla, California, United States
Collaborative Neuroscience Research Site Number : 8400045
Los Alamitos, California, United States
Multiple Sclerosis Center- Site Number : 8400143
Los Angeles, California, United States
Multiple Sclerosis Center of California Site Number : 8400135
Newport Beach, California, United States
SC3 Research - Pasadena Site Number : 8400070
Pasadena, 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
Advanced Neurosciences Research Site Number : 8400025
Fort Collins, Colorado, United States
South Florida Neurology Associates Site Number : 8400029
Boca Raton, Florida, United States
MS & Neuromuscular Center of Excellence Site Number : 8400172
Clearwater, Florida, United States
University of Florida, Fixel Center for Neurology Site Number : 8400159
Gainesville, Florida, United States
Neurology Associates, PA- Site Number : 8400004
Maitland, Florida, United States
University of South Florida Site Number : 8400006
Tampa, Florida, United States
Velocity Clinical Research Site Number : 8400003
Savannah, Georgia, United States
Hawaii Pacific Neuroscience Site Number : 8400103
Honolulu, Hawaii, United States
Consultants In Neurology- Site Number : 8400011
Northbrook, Illinois, United States
Methodist Hospital Site Number : 8400164
Merrillville, Indiana, United States
College Park Family Care Center Site Number : 8400044
Overland Park, Kansas, United States
University of Kentucky Site Number : 8400106
Lexington, Kentucky, United States
Ochsner Baptist Clinical Trials Unit (CTU)- Site Number : 8400107
New Orleans, Louisiana, United States
International Neurorehabilitation Institute Site Number : 8400034
Lutherville, Maryland, United States
Tufts Medical Center Site Number : 8400072
Boston, Massachusetts, United States
University of Massachusetts Site Number : 8400014
Worcester, 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
Mayo Clinic Site Number : 8400111
Rochester, Minnesota, United States
Sharlin Health & Neurology Site Number : 8400093
Ozark, Missouri, 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
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
Duke Neurological Disorders Clinic- Site Number : 8400098
Durham, North Carolina, United States
Meridian Clinical Research, LLC- Site Number : 8400005
Raleigh, North Carolina, United States
Atrium Health Wake Forest Baptist Site Number : 8400116
Winston-Salem, North Carolina, United States
Riverhills Neuroscience - Norwood Site Number : 8400167
Cincinnati, Ohio, United States
Cleveland Clinic Site Number : 8400125
Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center- Site Number : 8400150
Columbus, Ohio, United States
The Boster Center for Multiple Sclerosis Site Number : 8400147
Columbus, Ohio, United States
Providence Multiple Sclerosis Center Site Number : 8400020
Portland, Oregon, United States
Jefferson Neurology Associates Site Number : 8400016
Philadelphia, Pennsylvania, United States
Mountain View Clinical Research Site Number : 8400024
Greer, South Carolina, 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
Investigational Site Number : 0320002
Caba, Buenos Aires, Argentina
Investigational Site Number : 0320003
Rosario, Santa Fe, Argentina
Investigational Site Number : 0360005
Concord, New South Wales, Australia
Investigational Site Number : 0360006
St Leonards, New South Wales, Australia
Investigational Site Number : 0360003
Hobart, Tasmania, Australia
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 : 0560009
Bruxelles, Belgium
Investigational Site Number : 0560004
Gent, Belgium
Investigational Site Number : 0560008
Liège, Belgium
Investigational Site Number : 0560001
Pelt, Belgium
Investigational Site Number : 0560007
Sint-Lambrechts-Woluwe, Belgium
Instituto de Neurologia de Curitiba Site Number : 0760002
Curitiba, Paraná, Brazil
CPQuali Pesquisa Clinica Site Number : 0760007
Sao Paulo, São Paulo, Brazil
Investigational Site Number : 1000002
Pleven, Bulgaria
Investigational Site Number : 1000004
Sofia, Bulgaria
Investigational Site Number : 1000008
Sofia, Bulgaria
Investigational Site Number : 1000001
Sofia, Bulgaria
Investigational Site Number : 1000011
Sofia, Bulgaria
Investigational Site Number : 1240002
Edmonton, Alberta, Canada
Investigational Site Number : 1240016
Vancouver, British Columbia, Canada
Investigational Site Number : 1240012
Hamilton, Ontario, Canada
Investigational Site Number : 1240003
Ottawa, Ontario, Canada
Investigational Site Number : 1240013
Toronto, Ontario, 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 : 1240001
Quebec, Canada
Investigational Site Number : 1240021
Quebec, Canada
Investigational Site Number : 1520002
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520001
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1560003
Beijing, China
Investigational Site Number : 1560012
Beijing, China
Investigational Site Number : 1560009
Beijing, China
Investigational Site Number : 1560025
Beijing, China
Investigational Site Number : 1560004
Changchun, China
Investigational Site Number : 1560015
Changsha, China
Investigational Site Number : 1560005
Chengdu, China
Investigational Site Number : 1560035
Fuzhou, China
Investigational Site Number : 1560002
Guangzhou, China
Investigational Site Number : 1560027
Hohhot, China
Investigational Site Number : 1560001
Shanghai, China
Investigational Site Number : 1560008
Taiyuan, China
Investigational Site Number : 1560026
Wenzhou, China
Investigational Site Number : 1700001
Bogota, Colombia
Investigational Site Number : 1700003
Bogotá, Colombia
Investigational Site Number : 1910001
Zagreb, Croatia
Investigational Site Number : 1910002
Zagreb, Croatia
Investigational Site Number : 2030002
Brno, Czechia
Investigational Site Number : 2030004
Hradec Kralove, Czechia
Investigational Site Number : 2030001
Jihlava, Czechia
Investigational Site Number : 2030003
Teplice, Czechia
Investigational Site Number : 2080001
Esbjerg, Denmark
Investigational Site Number : 2080005
Holstebro, Denmark
Investigational Site Number : 2330001
Tallinn, Estonia
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 : 2500017
Nimes, France
Investigational Site Number : 2500014
Paris, 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 : 2500012
Toulouse, France
Investigational Site Number : 2680005
Tbilisi, Georgia
Investigational Site Number : 2680009
Tbilisi, Georgia
Investigational Site Number : 2680003
Tbilisi, Georgia
Investigational Site Number : 2680004
Tbilisi, Georgia
Investigational Site Number : 2760005
Bayreuth, Germany
Investigational Site Number : 2760009
Berlin, Germany
Investigational Site Number : 2760015
Berlin, Germany
Investigational Site Number : 2760020
Bochum, Germany
Investigational Site Number : 2760001
Dresden, Germany
Investigational Site Number : 2760021
Düsseldorf, Germany
Investigational Site Number : 2760012
Essen, Germany
Investigational Site Number : 2760002
Gießen, Germany
Investigational Site Number : 2760006
Hannover, Germany
Investigational Site Number : 2760018
München, 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 : 3000004
Larisa, Greece
Investigational Site Number : 3000007
Maroussi, Greece
Investigational Site Number : 3000003
Thessaloniki, Greece
Investigational Site Number : 3000009
Thessaloniki, Greece
Investigational Site Number : 3480206
Budapest, Hungary
Investigational Site Number : 3480202
Budapest, Hungary
Investigational Site Number : 3480203
Budapest, Hungary
Investigational Site Number : 3560014
Bengaluru, India
Investigational Site Number : 3560004
Mangaluru, India
Investigational Site Number : 3560005
New Delhi, India
Investigational Site Number : 3760008
Jerusalem, Israel
Investigational Site Number : 3760001
Ramat Gan, Israel
Investigational Site Number : 3760004
Safed, Israel
Investigational Site Number : 3800002
Pozzilli, Isernia, Italy
Investigational Site Number : 3800007
Cagliari, Italy
Investigational Site Number : 3800015
Catania, Italy
Investigational Site Number : 3800018
Chieti, Italy
Investigational Site Number : 3800016
Firenze, Italy
Investigational Site Number : 3800001
Milano, Italy
Investigational Site Number : 3800003
Napoli, Italy
Investigational Site Number : 3800006
Napoli, 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 : 3920022
Morioka-shi, Iwate, Japan
Investigational Site Number : 3920023
Sagamihara-shi, Kanagawa, 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 : 3920014
Bunkyo-ku, Tokyo, Japan
Investigational Site Number : 3920003
Kodaira-shi, Tokyo, Japan
Investigational Site Number : 3920010
Ota-ku, Tokyo, Japan
Investigational Site Number : 3920017
Shinjuku-ku, Tokyo, Japan
Investigational Site Number : 3920015
Toyama-shi, Toyama, Japan
Investigational Site Number : 4280002
Riga, Latvia
Investigational Site Number : 4840004
Guadalajara, Jalisco, Mexico
Investigational Site Number : 4840001
Cdmx, México, Mexico
Investigational Site Number : 4840005
Mexico city, Mexico
Investigational Site Number : 4840007
Tlalnepantla, Mexico
Investigational Site Number : 4840003
Veracruz, Mexico
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 : 5780005
Tromsø, Norway
Investigational Site Number : 6040004
Lima, Peru
Investigational Site Number : 6160003
Bydgoszcz, Kujawsko-pomorskie, Poland
Investigational Site Number : 6160001
Lodz, Lódzkie, Poland
Investigational Site Number : 6160005
Warszawa, Mazowieckie, Poland
Investigational Site Number : 6160006
Warszawa, Mazowieckie, Poland
Investigational Site Number : 6160007
Katowice, Slaskie, Poland
Investigational Site Number : 6160004
Katowice, Slaskie, Poland
Investigational Site Number : 6200001
Braga, Portugal
Investigational Site Number : 6200007
Lisboa, Portugal
Investigational Site Number : 6200012
Lisboa, Portugal
Investigational Site Number : 6200002
Matosinhos, Portugal
Investigational Site Number : 6200010
Porto, Portugal
Investigational Site Number : 6200004
Santa Maria da Feira, Portugal
Investigational Site Number : 6420008
Bucuresti, Romania
Investigational Site Number : 6420004
Campulung Muscel, Romania
Investigational Site Number : 6420003
Constanta, Romania
Investigational Site Number : 6420013
Oradea, Romania
Investigational Site Number : 6420001
Targu Mures, Romania
Investigational Site Number : 6420002
Timișoara, Romania
Investigational Site Number : 6430018
Barnaul, Russian Federation
Investigational Site Number : 6430022
Ekaterinburg, Russian Federation
Investigational Site Number : 6430023
Kaliningrad, Russian Federation
Investigational Site Number : 6430004
Kazan, Russian Federation
Investigational Site Number : 6430021
Krasnoyarsk, Russian Federation
Investigational Site Number : 6430013
Moscow, Russian Federation
Investigational Site Number : 6430011
Moscow, Russian Federation
Investigational Site Number : 6430014
Nizhny Novgorod, Russian Federation
Investigational Site Number : 6430008
Pyatigorsk, Russian Federation
Investigational Site Number : 6430015
Rostov-on-Don, Russian Federation
Investigational Site Number : 6430017
Saint-Petersburg, Russian Federation
Investigational Site Number : 6430009
Samara, Russian Federation
Investigational Site Number : 6430020
Saransk, Russian Federation
Investigational Site Number : 6430007
Tyumen, Russian Federation
Investigational Site Number : 6430006
Ufa, Russian Federation
Investigational Site Number : 6880001
Belgrade, Serbia
Investigational Site Number : 6880002
Kragujevac, Serbia
Investigational Site Number : 7100001
Pretoria, South Africa
Investigational Site Number : 7240012
La Coruña, A Coruña [La Coruña], Spain
Investigational Site Number : 7240015
Santiago de Compostela, A Coruña [La Coruña], Spain
Investigational Site Number : 7240007
Sevilla, Andalucia, Spain
Investigational Site Number : 7240010
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240013
Bilbao, Bizkaia, Spain
Investigational Site Number : 7240011
Salt, Girona [Gerona], Spain
Investigational Site Number : 7240016
Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number : 7240002
Majadahonda, Madrid, Spain
Investigational Site Number : 7240001
Pozuelo De Alarcón, Madrid, Spain
Investigational Site Number : 7240004
Córdoba, Spain
Investigational Site Number : 7240003
Madrid, Spain
Investigational Site Number : 7240005
Malaga, Spain
Investigational Site Number : 7240006
Murcia, Spain
Investigational Site Number : 7240014
Palma de Mallorca, Spain
Investigational Site Number : 7240008
Valencia, Spain
Investigational Site Number : 7520001
Göteborg, Sweden
Investigational Site Number : 7520005
Motala, Sweden
Investigational Site Number : 7640001
Bangkok, Thailand
Investigational Site Number : 7920009
Ankara, Turkey
Investigational Site Number : 7920014
Ankara, Turkey
Investigational Site Number : 7920005
Eskisehir, Turkey
Investigational Site Number : 7920010
Hatay, Turkey
Investigational Site Number : 7920016
Istanbul, Turkey
Investigational Site Number : 7920003
Istanbul, Turkey
Investigational Site Number : 7920002
Istanbul, Turkey
Investigational Site Number : 7920007
Istanbul, Turkey
Investigational Site Number : 7920015
Izmir, Turkey
Investigational Site Number : 7920018
Izmir, Turkey
Investigational Site Number : 7920001
Izmit, Turkey
Investigational Site Number : 7920017
Konya, Turkey
Investigational Site Number : 7920011
Kutahya, Turkey
Investigational Site Number : 7920012
Mersin, Turkey
Investigational Site Number : 7920013
Samsun, Turkey
Investigational Site Number : 8040020
Chernivtsi, Ukraine
Investigational Site Number : 8040012
Ivano-Frankivsk, Ukraine
Investigational Site Number : 8040017
Kharkiv, Ukraine
Investigational Site Number : 8040025
Kharkiv, Ukraine
Investigational Site Number : 8040023
Kharkiv, Ukraine
Investigational Site Number : 8040014
Kyiv, Ukraine
Investigational Site Number : 8040013
Kyiv, Ukraine
Investigational Site Number : 8040015
Kyiv, Ukraine
Investigational Site Number : 8040011
Lutsk, Ukraine
Investigational Site Number : 8040002
Lviv, Ukraine
Investigational Site Number : 8040007
Lviv, Ukraine
Investigational Site Number : 8040010
Odesa, Ukraine
Investigational Site Number : 8040024
Vinnytsya, Ukraine
Investigational Site Number : 8260003
Exeter, Devon, United Kingdom
Investigational Site Number : 8260016
Canterbury, Kent, United Kingdom
Investigational Site Number : 8260006
London, London, City Of, United Kingdom
Investigational Site Number : 8260005
London, London, City Of, 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 : 8260001
Cardiff, Vale Of Glamorgan, The, United Kingdom
Investigational Site Number : 8260009
Bristol, United Kingdom
Investigational Site Number : 8260019
Salford, United Kingdom
Investigational Site Number : 8260007
Sheffield, United Kingdom
Clinical Sciences & Operations, Study Director
Sanofi