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

July 1, 2025 updated by: Sanofi

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

Completed

Conditions

Non-relapsing Secondary Progressive Multiple Sclerosis

Intervention / Treatment

Detailed Description

This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 47months).

Participants with 6-month confirmed disability progression (CDP) had an option to receive tolebrutinib in the open-label (OL).

Study Type

Interventional

Enrollment (Actual)

1131

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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
- New South Wales
  - St Leonards, New South Wales, Australia, 2065
    - Investigational Site Number : 0360007
- 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
  - Bruxelles, Belgium, 1070
    - Investigational Site Number : 0560009
  - Edegem, Belgium, B-2650
    - Investigational Site Number :0560003
  - Gent, Belgium, 9000
    - Investigational Site Number : 0560004
  - 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
  - Quebec, Canada, G1J 1Z4
    - Investigational Site Number : 1240001
- 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
  - Nagpur, India, 440012
    - Investigational Site Number : 3560009
  - 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

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.
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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Triple

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Placebo tablet to match SAR442168 once daily	Drug: Placebo to match Tolebrutinib Pharmaceutical form: Film-coated tablet Route of administration: Oral
Experimental: SAR442168 60 mg of oral SAR442168 once daily	Drug: Tolebrutinib Pharmaceutical form: Film-coated tablet Route of administration: Oral Other Names: SAR442168

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS) Time Frame: Baseline (Day 1) up to approximately 47 months	The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis [MS]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of >=1.0 point from the baseline EDSS score when the baseline score was <=5.0 or of >=0.5 points when the baseline EDSS score was >5.0 confirmed after a minimum 6-month interval.	Baseline (Day 1) up to approximately 47 months

Secondary Outcome Measures

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

EFC16645 Plain language Results Summary

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2020

Primary Completion (Actual)

August 29, 2024

Study Completion (Actual)

August 29, 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)

July 2, 2025

Last Update Submitted That Met QC Criteria

July 1, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

EFC16645
U1111-1246-7768 (Registry Identifier: ICTRP)
2020-000647-30 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Outcome Measure	Measure Description	Time Frame
Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale Time Frame: Baseline (Day 1) up to approximately 47 months	The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 3-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score (of >=1.0 point from the baseline EDSS score when the baseline score is <=5.0, of >=0.5 points when the baseline EDSS score is >5.0) confirmed after a minimum 3-month interval. The confirmation of 3-month CDP followed the same criteria as that of 6-month CDP.	Baseline (Day 1) up to approximately 47 months
Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year Time Frame: Baseline (Day 1) up to approximately 47 months	Magnetic resonance imaging (MRI) of the brain was performed to identify number of new and/or enlarging T2-hyperintense lesions defined as the sum of the individual number of new and/or enlarging T2 lesions from baseline up to and including the EOS visit.	Baseline (Day 1) up to approximately 47 months
Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 Months Time Frame: Baseline (Day 1) up to approximately 47 months	The 9-HPT is a brief, standardized, quantitative test of upper extremity function and the time to complete the 9-HPT is used to assess a participant's manual dexterity and fine motor skills. A participant was asked to place the pegs into the holes and remove them with the dominant and non-dominant hand; two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs was recorded for each trial (ranging from 10 to 300 seconds). The mean time to test completion served for assessment of the participant's hand dexterity. Higher value indicated worse outcome. An increase of >20% from the baseline in the 9-HPT was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented.	Baseline (Day 1) up to approximately 47 months
Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 Months Time Frame: Baseline (Day 1) up to approximately 47 months	The T25-FW test is a quantitative mobility and leg function performance test used to assess a participant's walking ability. A participant was directed to one end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as safely possible for 2 trials. The amount of time (in seconds) to walk 25 feet was recorded (ranging from 2.2 to 180 seconds). The mean walk time was used for assessment of the participant's walking ability. Higher value indicated worse outcome. An increase of >20% from the baseline in the T25-FW test was considered meaningful worsening; time to onset of sustained 20% increase for at least 3 months is presented.	Baseline (Day 1) up to approximately 47 months
Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale Time Frame: Baseline (Day 1) up to approximately 47 months	The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. CDI was defined as a >=1 point decrease in the EDSS score from baseline confirmed over at least 6 months.	Baseline (Day 1) up to approximately 47 months
Percent Change in Brain Volume at EOS Compared to Month 6 Time Frame: Month 6 to EOS (up to approximately 47 months)	MRI of the brain was performed to evaluate percent change in brain volume which is considered as a marker of the central nervous system degenerative process. Least squares (LS) mean is presented.	Month 6 to EOS (up to approximately 47 months)
Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	The SDMT is used to assess processing speed, divided attention, visual scanning, tracking and motor speed. It involves a simple substitution task using a reference key. The number of correct substitutions and number of items completed within a 90 second interval (maximum 110 seconds) are recorded. A decrease of 4 points from baseline on the SDMT is considered meaningful worsening. The score was the number of correctly coded items from 0-110 in 90 seconds; higher scores indicated better outcome. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)
Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	The CVLT-II is a verbal learning and memory test consisting of recall and recognition of a list of 16 words. The list was read by the examiner, participants listened to the list and reported as many of the items as possible. For each assessment, 5 trials were completed. Standardized scores were used for analysis. The maximum possible score was 80 and a minimum was 0. A higher score indicated better recall meaning improved cognitive function. LS mean is presented. Baseline was defined as the last available value prior to the first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)
Change From Baseline in Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire Score at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	MSQoL-54 is standardized instrument with generic and MS-specific items which generates 12 subscales & 2 single-item measures (satisfaction with sexual function [1 item] & change in health [1 item].12 subscales are as follows:a:physical health (10 items),b:health perceptions (5 items), c:energy (5 items),d:role limitation physical (4 items),e:sexual function (4 items),f:pain (3 items),g:social function (3 items),h:health distress (4 items),i:overall quality of life (2 items),j:emotional well-being (5 items),k:role limitations emotional (3 items) and l:cognitive function (4 items).Physical health composite score was calculated as weighted sum of 'a to h' subscales and mental health composite score was calculated as weighted sum of 'i to l' subscales mentioned above.Each composite score was transformed linearly to common 0 (worst) to 100 (best) score range;LS mean is presented.Higher score indicated improved QoL.Baseline:last available value prior to first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)
Number of Participants With Treatment-emergent Adverse Events (AEs), Treatment-emergent Serious AEs, Treatment-emergent AEs Leading to Permanent Study Intervention Discontinuation, and Treatment-emergent Adverse Events of Special Interest (AESIs) Time Frame: From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.	From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months
Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite Time Frame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12	Blood samples were collected at specified timepoints to assess Cmax of tolebrutinib and M2 metabolite using a population pharmacokinetics (PopPK) model.	30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite Time Frame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12	Blood samples were collected at specified timepoints to assess Tmax of tolebrutinib and M2 metabolite using a PopPK model.	30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite Time Frame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12	Blood samples were collected at specified timepoints to assess AUC0-24 of tolebrutinib and M2 metabolite using a PopPK model.	30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	Blood samples were collected at specified timepoints to assess change from baseline in NfL and Chi3L1. Baseline was defined as the last available value prior to the first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)
Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	Blood samples were collected at specified timepoints to assess change from baseline in CD19+ B cells. Baseline was defined as the last available value prior to the first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)
Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS Time Frame: Baseline (Day 1) to EOS (up to approximately 47 months)	Blood samples were collected at specified timepoints to assess change from baseline in IgG and IgM levels. Baseline was defined as the last available value prior to the first dose of study intervention.	Baseline (Day 1) to EOS (up to approximately 47 months)

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

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

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Investigators

Publications and helpful links

Helpful Links

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Actual)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on Non-relapsing Secondary Progressive Multiple Sclerosis

Clinical Trials on Tolebrutinib

Search Similar Trials

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Medical Conditions

Drug Interventions

CROs by country

CROs in Iran

Conditions

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