AzTrials
AzTrials

Non-relapsing Secondary Progressive Multiple SclerosisPhase 3HERCULESNCT04411641

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

A Phase 3 study testing Tolebrutinib in people with Non-relapsing Secondary Progressive Multiple Sclerosis, run by Sanofi at 306 sites in 31 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Primary Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS Secondary Objective: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Tolebrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,131 participants
Where
306 sitesin 31 countries
Study dates
24 Sep 2020to 29 Aug 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

306 sites in 31 countries.

306 sites in 31 countries

United States51 sites

  • University of New Mexico-Site Number:8400032

    Albuquerque, New Mexico, 87131

  • Arcadia Neurology Center-Site Number:8400070

    Arcadia, California, 91006

  • Mountain Neurological Research Center, Inc.-Site Number:8400128

    Basalt, Colorado, 81621

  • University of Alabama MS Center-Site Number:8400013

    Birmingham, Alabama, 35233

  • South Florida Neurology Associates-Site Number:8400029

    Boca Raton, Florida, 33487

  • Tufts Medical Center-Site Number:8400072

    Boston, Massachusetts, 02111

  • University Of Vermont College Of Medicine-Site Number:8400130

    Burlington, Vermont, 05401

  • University Hospitals CMC-Site Number:8400083

    Cleveland, Ohio, 44106

  • Cleveland Clinic-Site Number:8400125

    Cleveland, Ohio, 44195

  • Optimed Research, LTD-Site Number:8400147

    Columbus, Ohio, 43235

  • Neurology Clinic, PC-Site Number:8400087

    Cordova, Tennessee, 38018

  • Neurology Specialists-Site Number:8400002

    Dayton, Ohio, 45417

  • University of Colorado-Site Number:8400012

    Denver, Colorado, 80262

  • Wayne State University-Site Number:8400046

    Detroit, Michigan, 48201

  • Sanford Brain & Spine Center-Site Number:8400126

    Fargo, North Dakota, 58103

  • Advanced Neurosciences Research-Site Number:8400025

    Fort Collins, Colorado, 80528

  • Advanced Neuroscience Center-Site Number:8400035

    Franklin, Tennessee, 37064

  • Premier Neurology-Site Number:8400069

    Greer, South Carolina, 29650

  • Mountain View Clinical Research-Site Number:8400024

    Greer, South Carolina, 29651-1817

  • Baylor College of Medicine-Site Number:8400136

    Houston, Texas, 77030

  • University of Kansas Medical Center-Site Number:8400023

    Kansas City, Kansas, 66160-7321

  • UC San Diego ACTRI-Site Number:8400101

    La Jolla, California, 92037

  • Lou Ruvo Center for Brain Health-Site Number:8400117

    Las Vegas, Nevada, 89106

  • CHI Saint Joseph Medical Group Neurology-Site Number:8400110

    Lexington, Kentucky, 40509

  • Collaborative Neuroscience Research-Site Number:8400045

    Long Beach, California, 90806

  • Multiple Sclerosis Center-Site Number:8400143

    Los Angeles, California, 90033

  • Neurology Associates, PA-Site Number:8400004

    Maitland, Florida, 32761

  • Medical College of Wisconsin-Site Number:8400028

    Milwaukee, Wisconsin, 53226

  • Minneapolis Clinic of Neurology-Site Number:8400051

    Minneapolis, Minnesota, 55422

  • Aqualane Clinical Research-Site Number:8400027

    Naples, Florida, 34105

  • Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038

    New York, New York, 10029-6501

  • Consultants In Neurology-Site Number:8400011

    Northbrook, Illinois, 60062

  • The Memorial Hospital-Site Number:8400033

    Owosso, Michigan, 48867

  • Perelman Center for Advanced Medicine-Site Number:8400142

    Philadelphia, Pennsylvania, 19104

  • Jefferson Neurology Associates-Site Number:8400016

    Philadelphia, Pennsylvania, 19107

  • Center for Neurology and Spine-Site Number:8400089

    Phoenix, Arizona, 84018

  • Providence Multiple Sclerosis Center-Site Number:8400020

    Portland, Oregon, 97225

  • Meridian Clinical Research, LLC-Site Number:8400005

    Raleigh, North Carolina, 27607

  • Mayo Clinic-Site Number:8400111

    Rochester, Minnesota, 55905

  • Neurology Center of San Antonio-Site Number:8400036

    San Antonio, Texas, 78258

  • University of San Francisco, Sandler Neurosciences Center-Site Number:8400137

    San Francisco, California, 94158

  • Meridian Clinical Research-Site Number:8400003

    Savannah, Georgia, 31406

  • Missouri Baptist Medical Center-Site Number:8400019

    St Louis, Missouri, 63131

  • Neurology Associates of Stony Brook-Site Number:8400042

    Stony Brook, New York, 11794

  • Axiom Clinical Research of Florida-Site Number:8400001

    Tampa, Florida, 33609-4052

  • University of South Florida-Site Number:8400006

    Tampa, Florida, 33612

  • Holy Name Hospital-Site Number:8400104

    Teaneck, New Jersey, 07666

  • Harbor UCLA-Site Number:8400088

    Torrance, California, 90502

  • Regina Berkovich, MD, PhD-Site Number:8400059

    West Hollywood, California, 90048

  • Columbus Neuroscience-Site Number:8400010

    Westerville, Ohio, 40382

  • University of Massachusetts-Site Number:8400014

    Worcester, Massachusetts, 01655

Other trials in United States

Russia25 sites

  • Investigational Site Number :6430018

    Barnaul, 656024

  • Investigational Site Number :6430025

    Kaliningrad, 236035

  • Investigational Site Number :6430003

    Kazan', 420021

  • Investigational Site Number :6430022

    Kemerovo, 650099

  • Investigational Site Number :6430017

    Kirov, 610998

  • Investigational Site Number :6430024

    Krasnoyarsk, 660029

  • Investigational Site Number :6430020

    Moscow, 117997

  • Investigational Site Number :6430002

    Moscow, 125367

  • Investigational Site Number :6430013

    Moscow, 127015

  • Investigational Site Number :6430001

    Moscow, 129110

  • Investigational Site Number :6430008

    Moscow, 129128

  • Investigational Site Number :6430021

    Nizhny Novgorod, 603137

  • Investigational Site Number :6430006

    Nizhny Novgorod, 603155

  • Investigational Site Number :6430005

    Novosibirsk, 630087

  • Investigational Site Number :6430026

    Perm, 614990

  • Investigational Site Number :6430007

    Pyatigorsk, 357538

  • Investigational Site Number :6430016

    Rostov-on-Don, 344022

  • Investigational Site Number :6430011

    Saint Petersburg, 197022

  • Investigational Site Number :6430004

    Saint Petersburg, 197110

  • Investigational Site Number :6430009

    Samara, 443095

  • Investigational Site Number :6430019

    Saransk, 430032

  • Investigational Site Number :6430014

    Smolensk, 214018

  • Investigational Site Number :6430012

    Tyumen, 625000

  • Investigational Site Number :6430010

    Ufa, 450005

  • Investigational Site Number :6430023

    Yekaterinburg, 620102

Other trials in Russia

Spain16 sites

  • Investigational Site Number :7240013

    Barcelona, Barcelona [Barcelona], 08035

  • Investigational Site Number :7240016

    Barcelona, Barcelona [Barcelona], 08036

  • Investigational Site Number :7240008

    Córdoba, 14004

  • Investigational Site Number :7240012

    Donostia / San Sebastian, Basque Country, 20014

  • Investigational Site Number :7240017

    Las Palmas de Gran Canaria, Las Palmas, 35010

  • Investigational Site Number :7240015

    Lleida, 25198

  • Investigational Site Number :7240005

    Madrid, 28007

  • Investigational Site Number :7240002

    Madrid, 28034

  • Investigational Site Number :7240003

    Madrid, 28040

  • Investigational Site Number :7240004

    Majadahonda, Madrid, 28222

  • Investigational Site Number :7240009

    Málaga, 29010

  • Investigational Site Number :7240010

    Murcia, 30120

  • Investigational Site Number :7240001

    Pozuelo de Alarcón, Madrid, 28223

  • Investigational Site Number :7240014

    Salt, Girona [Gerona], 17190

  • Investigational Site Number :7240007

    Seville, Andalusia, 41009

  • Investigational Site Number :7240011

    Valencia, 46026

Other trials in Spain

China15 sites

  • Investigational Site Number :1560006

    Beijing, 100034

  • Investigational Site Number :1560012

    Beijing, 100053

  • Investigational Site Number :1560021

    Beijing, 100700

  • Investigational Site Number :1560003

    Beijing, 100730

  • Investigational Site Number :1560009

    Beijing, 100730

  • Investigational Site Number :1560004

    Changchun, 130021

  • Investigational Site Number :1560015

    Changsha, 410008

  • Investigational Site Number :1560005

    Chengdu, 610041

  • Investigational Site Number :1560019

    Chongqing, 400016

  • Investigational Site Number :1560035

    Fuzhou, 350005

  • Investigational Site Number :1560001

    Guangzhou, 510630

  • Investigational Site Number :1560007

    Hangzhou, 310009

  • Investigational Site Number :1560014

    Shijiazhuang, 050000

  • Investigational Site Number :1560008

    Taiyuan, 030001

  • Investigational Site Number :1560017

    Xi'an, 710038

Other trials in China

France14 sites

  • Investigational Site Number :2500011

    Bron, 69500

  • Investigational Site Number :2500005

    Clermont-Ferrand, 63003

  • Investigational Site Number :2500015

    Gonesse, 95500

  • Investigational Site Number :2500009

    Lille, 59037

  • Investigational Site Number :2500006

    Montpellier, 34295

  • Investigational Site Number :2500008

    Nancy, 54035

  • Investigational Site Number :2500010

    Nantes, 44093

  • Investigational Site Number :2500017

    Nîmes, 30029

  • Investigational Site Number :2500016

    Paris, 75012

  • Investigational Site Number :2500014

    Paris, 75013

  • Investigational Site Number :2500007

    Paris, 75019

  • Investigational Site Number :2500003

    Rennes, 35033

  • Investigational Site Number :2500001

    Strasbourg, 67098

  • Investigational Site Number :2500012

    Toulouse, 31059

Other trials in France

Ukraine14 sites

  • Investigational Site Number :8040008

    Chernivtsi, 58000

  • Investigational Site Number :8040016

    Chernivtsi, 58023

  • Investigational Site Number :8040003

    Dnipro, 49005

  • Investigational Site Number :8040010

    Ivano-Frankivsk, 76018

  • Investigational Site Number :8040007

    Kharkiv, 61068

  • Investigational Site Number :8040011

    Kharkiv, 61103

  • Investigational Site Number :8040012

    Kharkiv, 61103

  • Investigational Site Number :8040013

    Kyiv, 03115

  • Investigational Site Number :8040005

    Lutsk, 43005

  • Investigational Site Number :8040009

    Lviv, 79010

  • Investigational Site Number :8040004

    Lviv, 79013

  • Investigational Site Number :8040002

    Odesa, 65025

  • Investigational Site Number :8040006

    Vinnytsia, 21050

  • Investigational Site Number :8040014

    Zhytomyr, 10002

Other trials in Ukraine

Italy12 sites

  • Investigational Site Number :3800011

    Bergamo, 24127

  • Investigational Site Number :3800007

    Cagliari, 09126

  • Investigational Site Number :3800012

    Florence, 50134

  • Investigational Site Number :3800016

    Florence, 50141

  • Investigational Site Number :3800014

    Genova, 16132

  • Investigational Site Number :3800013

    L’Aquila, 67010

  • Investigational Site Number :3800004

    Milan, 20122

  • Investigational Site Number :3800001

    Milan, 20132

  • Investigational Site Number :3800010

    Milan, 20133

  • Investigational Site Number :3800008

    Pavia, 27100

  • Investigational Site Number :3800005

    Roma, 00152

  • Investigational Site Number :3800009

    Roma, 00168

Other trials in Italy

Japan12 sites

  • Investigational Site Number :3920016

    Chiba, Chiba, 260-8677

  • Investigational Site Number :3920018

    Kawagoe-shi, Saitama, 350-8550

  • Investigational Site Number :3920003

    Kodaira-shi, Tokyo, 187-8551

  • Investigational Site Number :3920011

    Kyoto, Kyoto, 616-8255

  • Investigational Site Number :3920004

    Moriguchi-shi, Osaka, 570-8507

  • Investigational Site Number :3920022

    Morioka, Iwate, 020-8505

  • Investigational Site Number :3920005

    Niigata, Niigata, 951-8520

  • Investigational Site Number :3920001

    Osaka, Osaka, 556-0016

  • Investigational Site Number :3920010

    Ōta-ku, Tokyo, 146-0065

  • Investigational Site Number :3920023

    Sagamihara-shi, 252-0392

  • Investigational Site Number :3920020

    Sendai, Miyagi, 980-8574

  • Investigational Site Number :3920009

    Ube-shi, Yamaguchi, 755-8505

Other trials in Japan

Turkey (Türkiye)12 sites

  • Investigational Site Number :7920005

    Eskişehir

  • Investigational Site Number :7920010

    Hatay

  • Investigational Site Number :7920002

    Istanbul, 34098

  • Investigational Site Number :7920009

    Istanbul, 34688

  • Investigational Site Number :7920007

    Istanbul, 34785

  • Investigational Site Number :7920006

    Istanbul, 34896

  • Investigational Site Number :7920003

    Istanbul

  • Investigational Site Number :7920013

    Izmir, 35100

  • Investigational Site Number :7920001

    İzmit, 41380

  • Investigational Site Number :7920011

    Kütahya, 43100

  • Investigational Site Number :7920012

    Mersin, 33070

  • Investigational Site Number :7920008

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Canada11 sites

  • Investigational Site Number :1240017

    Burnaby, British Columbia, V5G 2X6

  • Investigational Site Number :1240006

    Gatineau, Quebec, J8Y 1W2

  • Investigational Site Number :1240005

    Greenfield Park, Quebec, J4V 2J2

  • Investigational Site Number :1240011

    Halifax, Nova Scotia, B3H 1V7

  • Investigational Site Number :1240004

    Montreal, Quebec, H2X 0A9

  • Investigational Site Number :1240015

    Montreal, Quebec, H3A 2B4

  • Investigational Site Number :1240003

    Ottawa, Ontario, K1H 8L6

  • Investigational Site Number : 1240001

    Québec, G1J 1Z4

  • Investigational Site Number :1240021

    Québec, G1W 4R4

  • Investigational Site Number :1240007

    Sherbrooke, Quebec, J1H 5N4

  • Investigational Site Number :1240008

    Toronto, Ontario, M4N 3M5

Other trials in Canada

United Kingdom11 sites

  • Investigational Site Number :8260009

    Bristol, BS10 5NB

  • Investigational Site Number :8260001

    Cardiff, CF4 4XY

  • Investigational Site Number :8260003

    Exeter, Devon, EX2 5DW

  • Investigational Site Number :8260005

    London, SW17 0RE

  • Investigational Site Number :8260018

    London, W6 8RF

  • Investigational Site Number :8260014

    Newcastle upon Tyne, NE1 4LP

  • Investigational Site Number :8260012

    Nottingham, Nottinghamshire, NG7 2UH

  • Investigational Site Number :8260013

    Oxford, Oxfordshire, OX3 9DZ

  • Investigational Site Number :8260008

    Plymouth, Devon, PL6 8DH

  • Investigational Site Number :8260019

    Salford, M6 8HD

  • Investigational Site Number :8260010

    Swansea, Neath Port Talbot, SA6 6NL

Other trials in United Kingdom

Germany10 sites

  • Investigational Site Number :2760005

    Bayreuth, 95445

  • Investigational Site Number :2760009

    Berlin, 10117

  • Investigational Site Number :2760001

    Dresden, 01307

  • Investigational Site Number :2760012

    Essen, 45147

  • Investigational Site Number :2760002

    Giessen, 35385

  • Investigational Site Number :2760010

    Halle, 06120

  • Investigational Site Number :2760006

    Hanover, 30625

  • Investigational Site Number :2760008

    Münster, 48149

  • Investigational Site Number :2760004

    Rostock, 18055

  • Investigational Site Number :2760011

    Ulm, 89081

Other trials in Germany

Poland10 sites

  • Investigational Site Number :6160003

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Investigational Site Number :6160002

    Katowice, Silesian Voivodeship, 40-571

  • Investigational Site Number :6160007

    Katowice, Silesian Voivodeship, 40-684

  • Investigational Site Number :6160004

    Katowice, Silesian Voivodeship, 40-686

  • Investigational Site Number :6160001

    Lodz, 90-549

  • Investigational Site Number :6160012

    Lublin, 20-016

  • Investigational Site Number :6160008

    Plewiska, Greater Poland Voivodeship, 62-064

  • Investigational Site Number :6160005

    Warsaw, Masovian Voivodeship, 01-211

  • Investigational Site Number :6160006

    Warsaw, Masovian Voivodeship, 01-684

  • Investigational Site Number :6160011

    Zabrze, 41-800

Other trials in Poland

Belgium8 sites

  • Investigational Site Number : 0560009

    Brussels, 1070

  • Investigational Site Number :0560007

    Brussels, 1200

  • Investigational Site Number :0560003

    Edegem, B-2650

  • Investigational Site Number : 0560004

    Ghent, 9000

  • Investigational Site Number :0560006

    Leuven, 3000

  • Investigational Site Number :0560008

    Liège, 4000

  • Investigational Site Number :0560002

    Mons, 7000

  • Investigational Site Number :0560001

    Overpelt, 3900

Other trials in Belgium

Romania8 sites

  • Investigational Site Number :6420008

    Bucharest, 022328

  • Investigational Site Number :6420004

    Campulung Muscel, 115100

  • Investigational Site Number :6420006

    Cluj-Napoca, 400012

  • Investigational Site Number :6420003

    Constanța, 900123

  • Investigational Site Number :6420013

    Oradea, 410154

  • Investigational Site Number :6420005

    Sibiu, 550052

  • Investigational Site Number :6420001

    Târgu Mureş, 540136

  • Investigational Site Number :6420002

    Timișoara, 300736

Other trials in Romania

Bulgaria7 sites

  • Investigational Site Number :1000002

    Pleven, 5800

  • Investigational Site Number :1000005

    Plovdiv, 4000

  • Investigational Site Number :1000004

    Sofia, 1113

  • Investigational Site Number :1000008

    Sofia, 1407

  • Investigational Site Number :1000001

    Sofia, 1431

  • Investigational Site Number :1000006

    Sofia, 1431

  • Investigational Site Number :1000009

    Sofia, 1680

Other trials in Bulgaria

Greece7 sites

  • Investigational Site Number :3000001

    Athens, 115 28

  • Investigational Site Number :3000006

    Athens, 11535

  • Investigational Site Number :3000002

    Athens, 12462

  • Investigational Site Number :3000007

    Athens, 15125

  • Investigational Site Number :3000004

    Larissa, 41110

  • Investigational Site Number :3000003

    Thessaloniki, 546 36

  • Investigational Site Number :3000005

    Thessaloniki, 57010

Other trials in Greece

India7 sites

  • Investigational Site Number :3560007

    Gūrgaon, 122001

  • Investigational Site Number :3560003

    Gūrgaon, 122002

  • Investigational Site Number :3560005

    India

  • Investigational Site Number :3560004

    Mangaluru, 575018

  • Investigational Site Number : 3560009

    Nagpur, 440012

  • Investigational Site Number :3560006

    New Delhi, 110029

  • Investigational Site Number :3560002

    New Delhi, 110060

Other trials in India

Australia6 sites

  • Investigational Site Number :0360001

    Fitzroy, Victoria, 3065

  • Investigational Site Number :0360006

    Heidelberg West, Victoria, 3081

  • Investigational Site Number :0360004

    Hobart, Tasmania, 7001

  • Investigational Site Number :0360002

    Kent Town, South Australia

  • Investigational Site Number : 0360007

    St Leonards, New South Wales, 2065

  • Investigational Site Number :0360003

    Woolloongabba, Queensland, 4102

Other trials in Australia

Czechia6 sites

  • Investigational Site Number :2030002

    Brno, 65691

  • Investigational Site Number :2030004

    Hradec Králové, 50005

  • Investigational Site Number :2030001

    Jihlava, 58633

  • Investigational Site Number :2030010

    Ostrava - Poruba, 70852

  • Investigational Site Number :2030005

    Prague, 12808

  • Investigational Site Number :2030003

    Teplice, 415 29

Other trials in Czechia

Hungary6 sites

  • Investigational Site Number :3480008

    Budapest, 1135

  • Investigational Site Number :3480004

    Budapest, 1145

  • Investigational Site Number :3480007

    Budapest, 1152

  • Investigational Site Number :3480002

    Pécs, 7623

  • Investigational Site Number :3480001

    Szeged, 6725

  • Investigational Site Number :3480006

    Tatabánya, 2800

Other trials in Hungary

Portugal6 sites

  • Investigational Site Number :6200001

    Braga, 4710-243

  • Investigational Site Number :6200011

    Lisbon, 1162-050

  • Investigational Site Number :6200007

    Lisbon, 1349-019

  • Investigational Site Number :6200006

    Lisbon, 1649-035

  • Investigational Site Number :6200002

    Matosinhos Municipality, 4464-513

  • Investigational Site Number :6200010

    Porto, 4099-001

Other trials in Portugal

Argentina5 sites

  • Investigational Site Number :0320007

    Buenos Aires, 1860

  • Investigational Site Number :0320001

    CABA, Buenos Aires F.D., C1061

  • Investigational Site Number :0320002

    Capital Federal, Buenos Aires, 1012

  • Investigational Site Number :0320006

    Córdoba, 5000

  • Investigational Site Number :0320005

    San Miguel de Tucumán, T4000AXL

Other trials in Argentina

Israel5 sites

  • Investigational Site Number :3760002

    Ashkelon, 78278

  • Investigational Site Number :3760003

    Haifa, 31096

  • Investigational Site Number :3760008

    Jerusalem, 91120

  • Investigational Site Number :3760004

    Safed, 13100

  • Investigational Site Number :3760001

    Tel HaShomer, 52621

Other trials in Israel

Austria4 sites

  • Investigational Site Number :0400003

    Innsbruck, 6020

  • Investigational Site Number :0400001

    Linz, 4020

  • Investigational Site Number :0400004

    Linz, 4021

  • Investigational Site Number :0400002

    Vienna, 1090

Other trials in Austria

Netherlands4 sites

  • Investigational Site Number :5280001

    Amsterdam, 1081 GN

  • Investigational Site Number :5280003

    Breda, 4818 CK

  • Investigational Site Number :5280006

    Groningen, 9728 NZ

  • Investigational Site Number :5280002

    Sittard-Geleen, 6162 BG

Other trials in Netherlands

Denmark3 sites

  • Investigational Site Number :2080001

    Esbjerg, 6700

  • Investigational Site Number :2080005

    Holstebro, 7500

  • Investigational Site Number :2080004

    Odense, 5000

Other trials in Denmark

Finland3 sites

  • Investigational Site Number :2460003

    Helsinki, 00180

  • Investigational Site Number :2460001

    Tampere, 33520

  • Investigational Site Number :2460002

    Turku, 20520

Other trials in Finland

Lithuania3 sites

  • Investigational Site Number :4400003

    Kaunas, 50161

  • Investigational Site Number :4400002

    Klaipėda, 92288

  • Investigational Site Number :4400001

    Vilnius, 08661

Other trials in Lithuania

Norway3 sites

  • Investigational Site Number :5780003

    Bergen, 5021

  • Investigational Site Number :5780002

    Namsos, 7800

  • Investigational Site Number :5780001

    Oslo, 0450

Other trials in Norway

Belarus2 sites

  • Investigational Site Number :1120004

    Vitebsk, 210009

  • Investigational Site Number :1120005

    Vitebsk, 210037

Other trials in Belarus

About this study

Official title: 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

Read the 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).

Being tested
Tolebrutinib, Placebo to match Tolebrutinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TolebrutinibDrug

    Also called SAR442168

    Pharmaceutical form: Film-coated tablet Route of administration: Oral

  • Placebo to match TolebrutinibDrug

    Pharmaceutical form: Film-coated tablet Route of administration: Oral

Study groups in NCT04411641
Study groupRoleWhat they receive
SAR442168Experimental60 mg of oral SAR442168 once daily
Receives: Drug: Tolebrutinib
PlaceboPlacebo comparatorPlacebo tablet to match SAR442168 once daily
Receives: Drug: Placebo to match Tolebrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)

    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.

    Measured: Baseline (Day 1) up to approximately 47 months

Secondary outcomes (16)

  1. Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale

    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.

    Measured: Baseline (Day 1) up to approximately 47 months

  2. Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year

    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.

    Measured: Baseline (Day 1) up to approximately 47 months

  3. Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 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.

    Measured: Baseline (Day 1) up to approximately 47 months

  4. Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 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.

    Measured: Baseline (Day 1) up to approximately 47 months

  5. Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale

    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.

    Measured: Baseline (Day 1) up to approximately 47 months

  6. Percent Change in Brain Volume at EOS Compared to Month 6

    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.

    Measured: Month 6 to EOS (up to approximately 47 months)

  7. Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

  8. Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

  9. Change From Baseline in Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire Score at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

  10. 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)

    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.

    Measured: From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months

  11. Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess Cmax of tolebrutinib and M2 metabolite using a population pharmacokinetics (PopPK) model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  12. Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess Tmax of tolebrutinib and M2 metabolite using a PopPK model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  13. Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess AUC0-24 of tolebrutinib and M2 metabolite using a PopPK model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  14. Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

  15. Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

  16. Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS

    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.

    Measured: Baseline (Day 1) to EOS (up to approximately 47 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2020
  2. Study start24 Sep 2020
  3. Primary completion29 Aug 2024
  4. Study completion29 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,131 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04411641
Sponsor's protocol ID
EFC16645
Other IDs
U1111-1246-7768, 2020-000647-30
Acronym
HERCULES
Status last verified
Jun 2025
First submitted
28 May 2020
Last updated
2 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Maxwell CR, Turner TJ, Wallstroem E, Patel S, Pappas SC, Lewis JH, Andrade RJ, Syed S. Tolebrutinib liver safety: A detailed overview. Mult Scler Relat Disord. 2026 Jul 23;113:107404. doi: 10.1016/j.msard.2026.107404. Online ahead of print.

    PubMed 42546561

  • Fox RJ, Bar-Or A, Traboulsee A, Oreja-Guevara C, Giovannoni G, Vermersch P, Syed S, Li Y, Vargas WS, Turner TJ, Wallstroem E, Reich DS; HERCULES Trial Group. Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis. N Engl J Med. 2025 May 15;392(19):1883-1892. doi: 10.1056/NEJMoa2415988. Epub 2025 Apr 8.

    PubMed 40202696

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tolebrutinib in people with Non-relapsing Secondary Progressive Multiple Sclerosis, run by Sanofi at 306 sites in 31 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 306 sites in United States, Russia, Spain, China, France and 26 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04411641, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.

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