Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (HERCULES)

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

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 Overview

• Status: Active, not recruiting
• Conditions: Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Tolebrutinib; Drug: Placebo to match Tolebrutinib

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.

• Study Type: Interventional
• Enrollment (Actual): 1131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1860
    • Investigational Site Number :0320007
  • Córdoba, Argentina, 5000
    • Investigational Site Number :0320006
  • San Miguel de Tucuman, Argentina, T4000AXL
    • Investigational Site Number :0320005
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1012
      • Investigational Site Number :0320002
  • Ciudad De Buenos Aires
    • Caba, Ciudad De Buenos Aires, Argentina, C1061
      • Investigational Site Number :0320001
• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Investigational Site Number :0360003
  • South Australia
    • Kent Town, South Australia, Australia
      • Investigational Site Number :0360002
  • Tasmania
    • Hobart, Tasmania, Australia, 7001
      • Investigational Site Number :0360004
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Investigational Site Number :0360001
    • Heidelberg West, Victoria, Australia, 3081
      • Investigational Site Number :0360006
• Austria
  • Innsbruck, Austria, 6020
    • Investigational Site Number :0400003
  • Linz, Austria, 4021
    • Investigational Site Number :0400004
  • Linz, Austria, 4020
    • Investigational Site Number :0400001
  • Wien, Austria, 1090
    • Investigational Site Number :0400002
• Belarus
  • Vitebsk, Belarus, 210009
    • Investigational Site Number :1120004
  • Vitebsk, Belarus, 210037
    • Investigational Site Number :1120005
• Belgium
  • Bruxelles, Belgium, 1200
    • Investigational Site Number :0560007
  • Edegem, Belgium, B-2650
    • Investigational Site Number :0560003
  • Leuven, Belgium, 3000
    • Investigational Site Number :0560006
  • Liège, Belgium, 4000
    • Investigational Site Number :0560008
  • Mons, Belgium, 7000
    • Investigational Site Number :0560002
  • Pelt, Belgium, 3900
    • Investigational Site Number :0560001
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Investigational Site Number :1000002
  • Plovdiv, Bulgaria, 4000
    • Investigational Site Number :1000005
  • Sofia, Bulgaria, 1113
    • Investigational Site Number :1000004
  • Sofia, Bulgaria, 1407
    • Investigational Site Number :1000008
  • Sofia, Bulgaria, 1431
    • Investigational Site Number :1000001
  • Sofia, Bulgaria, 1431
    • Investigational Site Number :1000006
  • Sofia, Bulgaria, 1680
    • Investigational Site Number :1000009
• Canada
  • Quebec, Canada, G1W 4R4
    • Investigational Site Number :1240021
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Investigational Site Number :1240017
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Investigational Site Number :1240011
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Investigational Site Number :1240003
    • Toronto, Ontario, Canada, M4N 3M5
      • Investigational Site Number :1240008
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Investigational Site Number :1240006
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Investigational Site Number :1240005
    • Montreal, Quebec, Canada, H2X 0A9
      • Investigational Site Number :1240004
    • Montreal, Quebec, Canada, H3A 2B4
      • Investigational Site Number :1240015
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Investigational Site Number :1240007
• China
  • Beijing, China, 100034
    • Investigational Site Number :1560006
  • Beijing, China, 100053
    • Investigational Site Number :1560012
  • Beijing, China, 100730
    • Investigational Site Number :1560009
  • Beijing, China, 100700
    • Investigational Site Number :1560021
  • Beijing, China, 100730
    • Investigational Site Number :1560003
  • Changchun, China, 130021
    • Investigational Site Number :1560004
  • Changsha, China, 410008
    • Investigational Site Number :1560015
  • Chengdu, China, 610041
    • Investigational Site Number :1560005
  • Chongqing, China, 400016
    • Investigational Site Number :1560019
  • Fuzhou, China, 350005
    • Investigational Site Number :1560035
  • Guangzhou, China, 510630
    • Investigational Site Number :1560001
  • Hangzhou, China, 310009
    • Investigational Site Number :1560007
  • Shijiazhuang, China, 050000
    • Investigational Site Number :1560014
  • Taiyuan, China, 030001
    • Investigational Site Number :1560008
  • Xi'an, China, 710038
    • Investigational Site Number :1560017
• Czechia
  • Brno, Czechia, 65691
    • Investigational Site Number :2030002
  • Hradec Kralove, Czechia, 50005
    • Investigational Site Number :2030004
  • Jihlava, Czechia, 58633
    • Investigational Site Number :2030001
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number :2030010
  • Praha 2, Czechia, 12808
    • Investigational Site Number :2030005
  • Teplice, Czechia, 415 29
    • Investigational Site Number :2030003
• Denmark
  • Esbjerg, Denmark, 6700
    • Investigational Site Number :2080001
  • Holstebro, Denmark, 7500
    • Investigational Site Number :2080005
  • Odense, Denmark, 5000
    • Investigational Site Number :2080004
• Finland
  • Helsinki, Finland, 00180
    • Investigational Site Number :2460003
  • Tampere, Finland, 33520
    • Investigational Site Number :2460001
  • Turku, Finland, 20520
    • Investigational Site Number :2460002
• France
  • Bron, France, 69500
    • Investigational Site Number :2500011
  • Clermont Ferrand, France, 63003
    • Investigational Site Number :2500005
  • Gonesse, France, 95500
    • Investigational Site Number :2500015
  • Lille, France, 59037
    • Investigational Site Number :2500009
  • Montpellier, France, 34295
    • Investigational Site Number :2500006
  • Nancy, France, 54035
    • Investigational Site Number :2500008
  • Nantes, France, 44093
    • Investigational Site Number :2500010
  • Nimes, France, 30029
    • Investigational Site Number :2500017
  • Paris, France, 75019
    • Investigational Site Number :2500007
  • Paris, France, 75012
    • Investigational Site Number :2500016
  • Paris, France, 75013
    • Investigational Site Number :2500014
  • Rennes, France, 35033
    • Investigational Site Number :2500003
  • Strasbourg, France, 67098
    • Investigational Site Number :2500001
  • Toulouse, France, 31059
    • Investigational Site Number :2500012
• Germany
  • Bayreuth, Germany, 95445
    • Investigational Site Number :2760005
  • Berlin, Germany, 10117
    • Investigational Site Number :2760009
  • Dresden, Germany, 01307
    • Investigational Site Number :2760001
  • Essen, Germany, 45147
    • Investigational Site Number :2760012
  • Gießen, Germany, 35385
    • Investigational Site Number :2760002
  • Halle (Saale), Germany, 06120
    • Investigational Site Number :2760010
  • Hannover, Germany, 30625
    • Investigational Site Number :2760006
  • Münster, Germany, 48149
    • Investigational Site Number :2760008
  • Rostock, Germany, 18055
    • Investigational Site Number :2760004
  • Ulm, Germany, 89081
    • Investigational Site Number :2760011
• Greece
  • Athens, Greece, 115 28
    • Investigational Site Number :3000001
  • Athens, Greece, 11535
    • Investigational Site Number :3000006
  • Athens, Greece, 12462
    • Investigational Site Number :3000002
  • Athens, Greece, 15125
    • Investigational Site Number :3000007
  • Larissa, Greece, 41110
    • Investigational Site Number :3000004
  • Thessaloniki, Greece, 546 36
    • Investigational Site Number :3000003
  • Thessaloniki, Greece, 57010
    • Investigational Site Number :3000005
• Hungary
  • Budapest, Hungary, 1135
    • Investigational Site Number :3480008
  • Budapest, Hungary, 1145
    • Investigational Site Number :3480004
  • Budapest, Hungary, 1152
    • Investigational Site Number :3480007
  • Pécs, Hungary, 7623
    • Investigational Site Number :3480002
  • Szeged, Hungary, 6725
    • Investigational Site Number :3480001
  • Tatabánya, Hungary, 2800
    • Investigational Site Number :3480006
• India
  • Gurgaon, India, 122001
    • Investigational Site Number :3560007
  • Gurgaon, India, 122002
    • Investigational Site Number :3560003
  • India, India
    • Investigational Site Number :3560005
  • Mangaluru, India, 575018
    • Investigational Site Number :3560004
  • New Delhi, India, 110060
    • Investigational Site Number :3560002
  • New Delhi, India, 110029
    • Investigational Site Number :3560006
• Israel
  • Ashkelon, Israel, 78278
    • Investigational Site Number :3760002
  • Haifa, Israel, 31096
    • Investigational Site Number :3760003
  • Jerusalem, Israel, 91120
    • Investigational Site Number :3760008
  • Tel HaShomer, Israel, 52621
    • Investigational Site Number :3760001
  • Zefat, Israel, 13100
    • Investigational Site Number :3760004
• Italy
  • Bergamo, Italy, 24127
    • Investigational Site Number :3800011
  • Cagliari, Italy, 09126
    • Investigational Site Number :3800007
  • Firenze, Italy, 50134
    • Investigational Site Number :3800012
  • Firenze, Italy, 50141
    • Investigational Site Number :3800016
  • Genova, Italy, 16132
    • Investigational Site Number :3800014
  • L'Aquila, Italy, 67010
    • Investigational Site Number :3800013
  • Milano, Italy, 20132
    • Investigational Site Number :3800001
  • Milano, Italy, 20133
    • Investigational Site Number :3800010
  • Milano, Italy, 20122
    • Investigational Site Number :3800004
  • Pavia, Italy, 27100
    • Investigational Site Number :3800008
  • Roma, Italy, 00152
    • Investigational Site Number :3800005
  • Roma, Italy, 00168
    • Investigational Site Number :3800009
• Japan
  • Sagamihara-shi, Japan, 252-0392
    • Investigational Site Number :3920023
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8677
      • Investigational Site Number :3920016
  • Iwate
    • Morioka-shi, Iwate, Japan, 020-8505
      • Investigational Site Number :3920022
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 616-8255
      • Investigational Site Number :3920011
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 980-8574
      • Investigational Site Number :3920020
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8520
      • Investigational Site Number :3920005
  • Osaka
    • Moriguchi-shi, Osaka, Japan, 570-8507
      • Investigational Site Number :3920004
    • Osaka-shi, Osaka, Japan, 556-0016
      • Investigational Site Number :3920001
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Investigational Site Number :3920018
  • Tokyo
    • Kodaira-shi, Tokyo, Japan, 187-8551
      • Investigational Site Number :3920003
    • Ota-ku, Tokyo, Japan, 146-0065
      • Investigational Site Number :3920010
  • Yamaguchi
    • Ube-shi, Yamaguchi, Japan, 755-8505
      • Investigational Site Number :3920009
• Lithuania
  • Kaunas, Lithuania, 50161
    • Investigational Site Number :4400003
  • Klaipeda, Lithuania, 92288
    • Investigational Site Number :4400002
  • Vilnius, Lithuania, 08661
    • Investigational Site Number :4400001
• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Investigational Site Number :5280001
  • Breda, Netherlands, 4818 CK
    • Investigational Site Number :5280003
  • Groningen, Netherlands, 9728 NZ
    • Investigational Site Number :5280006
  • Sittard-Geleen, Netherlands, 6162 BG
    • Investigational Site Number :5280002
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number :5780003
  • Namsos, Norway, 7800
    • Investigational Site Number :5780002
  • Oslo, Norway, 0450
    • Investigational Site Number :5780001
• Poland
  • Lodz, Poland, 90-549
    • Investigational Site Number :6160001
  • Lublin, Poland, 20-016
    • Investigational Site Number :6160012
  • Zabrze, Poland, 41-800
    • Investigational Site Number :6160011
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Investigational Site Number :6160003
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-211
      • Investigational Site Number :6160005
    • Warszawa, Mazowieckie, Poland, 01-684
      • Investigational Site Number :6160006
  • Slaskie
    • Katowice, Slaskie, Poland, 40-571
      • Investigational Site Number :6160002
    • Katowice, Slaskie, Poland, 40-686
      • Investigational Site Number :6160004
    • Katowice, Slaskie, Poland, 40-684
      • Investigational Site Number :6160007
  • Wielkopolskie
    • Plewiska, Wielkopolskie, Poland, 62-064
      • Investigational Site Number :6160008
• Portugal
  • Braga, Portugal, 4710-243
    • Investigational Site Number :6200001
  • Lisboa, Portugal, 1162-050
    • Investigational Site Number :6200011
  • Lisboa, Portugal, 1649-035
    • Investigational Site Number :6200006
  • Lisboa, Portugal, 1349-019
    • Investigational Site Number :6200007
  • Matosinhos, Portugal, 4464-513
    • Investigational Site Number :6200002
  • Porto, Portugal, 4099-001
    • Investigational Site Number :6200010
• Romania
  • Bucuresti, Romania, 022328
    • Investigational Site Number :6420008
  • Campulung, Romania, 115100
    • Investigational Site Number :6420004
  • Cluj-Napoca, Romania, 400012
    • Investigational Site Number :6420006
  • Constanta, Romania, 900123
    • Investigational Site Number :6420003
  • Oradea, Romania, 410154
    • Investigational Site Number :6420013
  • Sibiu, Romania, 550052
    • Investigational Site Number :6420005
  • Targu Mures, Romania, 540136
    • Investigational Site Number :6420001
  • Timisoara, Romania, 300736
    • Investigational Site Number :6420002
• Russian Federation
  • Barnaul, Russian Federation, 656024
    • Investigational Site Number :6430018
  • Ekaterinburg, Russian Federation, 620102
    • Investigational Site Number :6430023
  • Kaliningrad, Russian Federation, 236035
    • Investigational Site Number :6430025
  • Kazan, Russian Federation, 420021
    • Investigational Site Number :6430003
  • Kemerovo, Russian Federation, 650099
    • Investigational Site Number :6430022
  • Kirov, Russian Federation, 610998
    • Investigational Site Number :6430017
  • Krasnoyarsk, Russian Federation, 660029
    • Investigational Site Number :6430024
  • Moscow, Russian Federation, 125367
    • Investigational Site Number :6430002
  • Moscow, Russian Federation, 129128
    • Investigational Site Number :6430008
  • Moscow, Russian Federation, 117997
    • Investigational Site Number :6430020
  • Moscow, Russian Federation, 127015
    • Investigational Site Number :6430013
  • Moscow, Russian Federation, 129110
    • Investigational Site Number :6430001
  • Nizhny Novgorod, Russian Federation, 603137
    • Investigational Site Number :6430021
  • Nizhny Novgorod, Russian Federation, 603155
    • Investigational Site Number :6430006
  • Novosibirsk, Russian Federation, 630087
    • Investigational Site Number :6430005
  • Perm, Russian Federation, 614990
    • Investigational Site Number :6430026
  • Pyatigorsk, Russian Federation, 357538
    • Investigational Site Number :6430007
  • Rostov-on-Don, Russian Federation, 344022
    • Investigational Site Number :6430016
  • Saint-Petersburg, Russian Federation, 197110
    • Investigational Site Number :6430004
  • Samara, Russian Federation, 443095
    • Investigational Site Number :6430009
  • Saransk, Russian Federation, 430032
    • Investigational Site Number :6430019
  • Smolensk, Russian Federation, 214018
    • Investigational Site Number :6430014
  • St-Petersburg, Russian Federation, 197022
    • Investigational Site Number :6430011
  • Tyumen, Russian Federation, 625000
    • Investigational Site Number :6430012
  • Ufa, Russian Federation, 450005
    • Investigational Site Number :6430010
• Spain
  • Córdoba, Spain, 14004
    • Investigational Site Number :7240008
  • Lleida, Spain, 25198
    • Investigational Site Number :7240015
  • Madrid, Spain, 28034
    • Investigational Site Number :7240002
  • Madrid, Spain, 28007
    • Investigational Site Number :7240005
  • Madrid, Spain, 28040
    • Investigational Site Number :7240003
  • Murcia, Spain, 30120
    • Investigational Site Number :7240010
  • Málaga, Spain, 29010
    • Investigational Site Number :7240009
  • Valencia, Spain, 46026
    • Investigational Site Number :7240011
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Investigational Site Number :7240007
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number :7240013
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Investigational Site Number :7240016
  • Girona [Gerona]
    • Salt, Girona [Gerona], Spain, 17190
      • Investigational Site Number :7240014
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35010
      • Investigational Site Number :7240017
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Investigational Site Number :7240004
    • Pozuelo De Alarcón, Madrid, Spain, 28223
      • Investigational Site Number :7240001
  • Pais Vasco
    • Donostia, Pais Vasco, Spain, 20014
      • Investigational Site Number :7240012
• Turkey
  • Eskisehir, Turkey
    • Investigational Site Number :7920005
  • Hatay, Turkey
    • Investigational Site Number :7920010
  • Istanbul, Turkey, 34896
    • Investigational Site Number :7920006
  • Istanbul, Turkey, 34098
    • Investigational Site Number :7920002
  • Istanbul, Turkey, 34688
    • Investigational Site Number :7920009
  • Istanbul, Turkey, 34785
    • Investigational Site Number :7920007
  • Istanbul, Turkey
    • Investigational Site Number :7920003
  • Izmir, Turkey, 35100
    • Investigational Site Number :7920013
  • Izmit, Turkey, 41380
    • Investigational Site Number :7920001
  • Kütahya, Turkey, 43100
    • Investigational Site Number :7920011
  • Mersin, Turkey, 33070
    • Investigational Site Number :7920012
  • Trabzon, Turkey, 61080
    • Investigational Site Number :7920008
• Ukraine
  • Chernivtsi, Ukraine, 58000
    • Investigational Site Number :8040008
  • Chernivtsi, Ukraine, 58023
    • Investigational Site Number :8040016
  • Dnipro, Ukraine, 49005
    • Investigational Site Number :8040003
  • Ivano-Frankivsk, Ukraine, 76018
    • Investigational Site Number :8040010
  • Kharkiv, Ukraine, 61068
    • Investigational Site Number :8040007
  • Kharkiv, Ukraine, 61103
    • Investigational Site Number :8040011
  • Kharkiv, Ukraine, 61103
    • Investigational Site Number :8040012
  • Kyiv, Ukraine, 03115
    • Investigational Site Number :8040013
  • Lutsk, Ukraine, 43005
    • Investigational Site Number :8040005
  • Lviv, Ukraine, 79013
    • Investigational Site Number :8040004
  • Lviv, Ukraine, 79010
    • Investigational Site Number :8040009
  • Odesa, Ukraine, 65025
    • Investigational Site Number :8040002
  • Vinnytsia, Ukraine, 21050
    • Investigational Site Number :8040006
  • Zhytomyr, Ukraine, 10002
    • Investigational Site Number :8040014
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Investigational Site Number :8260009
  • Cardiff, United Kingdom, CF4 4XY
    • Investigational Site Number :8260001
  • London, United Kingdom, SW17 0RE
    • Investigational Site Number :8260005
  • London, United Kingdom, W6 8RF
    • Investigational Site Number :8260018
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Investigational Site Number :8260014
  • Salford, United Kingdom, M6 8HD
    • Investigational Site Number :8260019
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Investigational Site Number :8260003
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Investigational Site Number :8260008
  • Neath Port Talbot
    • Swansea, Neath Port Talbot, United Kingdom, SA6 6NL
      • Investigational Site Number :8260010
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Investigational Site Number :8260012
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DZ
      • Investigational Site Number :8260013
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama MS Center-Site Number:8400013
  • Arizona
    • Phoenix, Arizona, United States, 84018
      • Center for Neurology and Spine-Site Number:8400089
  • California
    • Arcadia, California, United States, 91006
      • Arcadia Neurology Center-Site Number:8400070
    • La Jolla, California, United States, 92037
      • UC San Diego ACTRI-Site Number:8400101
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research-Site Number:8400045
    • Los Angeles, California, United States, 90033
      • Multiple Sclerosis Center-Site Number:8400143
    • San Francisco, California, United States, 94158
      • University of San Francisco, Sandler Neurosciences Center-Site Number:8400137
    • Torrance, California, United States, 90502
      • Harbor UCLA-Site Number:8400088
    • West Hollywood, California, United States, 90048
      • Regina Berkovich, MD, PhD-Site Number:8400059
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Mountain Neurological Research Center, Inc.-Site Number:8400128
    • Denver, Colorado, United States, 80262
      • University of Colorado-Site Number:8400012
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research-Site Number:8400025
  • Florida
    • Boca Raton, Florida, United States, 33487
      • South Florida Neurology Associates-Site Number:8400029
    • Maitland, Florida, United States, 32761
      • Neurology Associates, PA-Site Number:8400004
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research-Site Number:8400027
    • Tampa, Florida, United States, 33612
      • University of South Florida-Site Number:8400006
    • Tampa, Florida, United States, 33609-4052
      • Axiom Clinical Research of Florida-Site Number:8400001
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research-Site Number:8400003
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Consultants In Neurology-Site Number:8400011
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • University of Kansas Medical Center-Site Number:8400023
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • CHI Saint Joseph Medical Group Neurology-Site Number:8400110
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center-Site Number:8400072
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts-Site Number:8400014
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University-Site Number:8400046
    • Owosso, Michigan, United States, 48867
      • The Memorial Hospital-Site Number:8400033
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology-Site Number:8400051
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic-Site Number:8400111
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center-Site Number:8400019
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Lou Ruvo Center for Brain Health-Site Number:8400117
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital-Site Number:8400104
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico-Site Number:8400032
  • New York
    • New York, New York, United States, 10029-6501
      • Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038
    • Stony Brook, New York, United States, 11794
      • Neurology Associates of Stony Brook-Site Number:8400042
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Meridian Clinical Research, LLC-Site Number:8400005
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Sanford Brain & Spine Center-Site Number:8400126
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals CMC-Site Number:8400083
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic-Site Number:8400125
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD-Site Number:8400147
    • Dayton, Ohio, United States, 45417
      • Neurology Specialists-Site Number:8400002
    • Westerville, Ohio, United States, 40382
      • Columbus Neuroscience-Site Number:8400010
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Multiple Sclerosis Center-Site Number:8400020
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Neurology Associates-Site Number:8400016
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine-Site Number:8400142
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Premier Neurology-Site Number:8400069
    • Greer, South Carolina, United States, 29651-1817
      • Mountain View Clinical Research-Site Number:8400024
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC-Site Number:8400087
    • Franklin, Tennessee, United States, 37064
      • Advanced Neuroscience Center-Site Number:8400035
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine-Site Number:8400136
    • San Antonio, Texas, United States, 78258
      • Neurology Center of San Antonio-Site Number:8400036
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University Of Vermont College Of Medicine-Site Number:8400130
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin-Site Number:8400028

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SAR442168; Dose 1 of oral SAR442168 once daily	Drug: Tolebrutinib; Pharmaceutical form: Film-coated tablet Route of administration: Oral; Other Names: SAR442168
PLACEBO_COMPARATOR: Placebo; Placebo tablet to match SAR442168 once daily	Drug: Placebo to match Tolebrutinib; Pharmaceutical form: Film-coated tablet Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month confirmed disability progression (CDP)	Time to onset of 6 months CDP defined as follows: -Increase of ≥1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is ≤5.0, or -Increase of ≥0.5 point when the baseline EDSS score is >5.0 -	Up to 48 approximately months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lymphocyte phenotype subsets	Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants	From Baseline up to approximately 48 months
Changes in serum Immunoglobulin level	Changes in serum Immunoglobulin level at the EOS compared to baseline	From Baseline up to approximately 48 months
3-months change in T25-FW and 9-HPT	Time to onset of composite CDP, confirmed over at least 3 months (3-month CCDP), by the EDSS Plus composite (EDSS score increase, or 20% increase in the T25 FW test, or 20% increase in the 9 hole peg test (9 HPT)	Up to approximately 48 months
3-month CDP	Time to onset of 3-month CDP as assessed by EDSS score	Up to approximately48 months
New and enlarging T2 hyperintense lesions by MRI	Total number of new or enlarging T2 hyperintense lesions as detected by MRI	From Baseline up to approximately 48 months
Time to onset of confirmed disability improvement (CDI)	Time to CDI defined as ≥1.0 point decrease on the EDSS score from baseline confirmed over at least 6 months	From Baseline up to approximately 48 months
Brain volume loss (BVL)	Percent change in Brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6	From 6 Months up to approximately 48 months
Change in cognitive function	Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) and by the California Verbal Learning Test (CVLT-II)	From Baseline up to approximately 48 months
Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54)	Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS	From Baseline up to approximately 48 months
Safety and Tolerability	Number of participants with adverse events (AEs), Serious AEs, AEs leading to permanent study intervention discontinuation, and adverse events of special interest (AESI)	From Screening until end of study up to approximately 48 months
Population pharmacokinetics	Plasma concentration of SAR442168 and relevant metabolites (population PK assessment) at Months 6, 9, and 12	Months 6, 9 and 12
Change in plasma neurofilament light chain (NfL)	Change in NfL levels at the EOS compared to baseline	From Baseline up to approximately 48 months
Change in serum chitinase-3 like protein 1 (Chi3L1)	Change in serum chitinase-3 like protein 1 (Chi3L1) at the EOS compared to baseline	From Baseline up to approximately 48 months

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 24, 2020
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (ACTUAL): June 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neoplastic Processes; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Neoplasm Metastasis
• Other Study ID Numbers: EFC16645; U1111-1246-7768 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No