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

Secondary Progressive Multiple Sclerosis Clinical Trial

— HERCULES  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04411641
• Other study ID #: EFC16645
• Secondary ID: U1111-1246-7768
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 24, 2020
• Est. completion date: August 2024

Study information

• Verified date: February 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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

Description:

Study duration will vary per participant in this event driven trial with a treatment duration of approximately 24 to 48 months.

Participants completing the treatment period will be proposed to enroll in a separate long term safety study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1131
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion criteria :

• 18 to 60 years of age inclusive

• Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria

• Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at screening

• The participant must have documented evidence of disability progression observed during the 12 months before screening

• Absence of clinical relapses for at least 24 months

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

• Is not a WOCBP OR

• Is a WOCBP and agrees to use an acceptable contraceptive method

Exclusion criteria:

• The participant has conditions that would adversely affect study participation such as short life expectancy.

• History of organ transplant.

• Evidence of infection with human immuodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation.

• Persistent chronic or active or recurring system infection, that may adversely affect participation or IMP administration in this study, as judged by the Investigator.

• History of malignancy within 5 years prior to screening.

• History of alcohol or drug abuse within 1 year prior to screening.

• Hospitalized for psychiatric disease within 2 years prior to screening.

• Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at screening

• Bleeding disorder, known platelet dysfunctionat any time prior to the screening visit

• A platelet count <150 000/µL at the screening visit

• A history of significant bleeding event within 6 months prior to screening, according to the Investigator's judgment such as, but not limited to cerebral or gastrointestinal bleeding.

• Lymphocyte count below the lower limit of normal at screening.

• Recent live (attenuated) vaccine within 2 months before the first treatment visit.

• Recent major surgery (within 4 weeks of screening) or planned major surgery during the study.

• The participant has received medications/treatments for MS within a specified time frame.

• Receiving potent and moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) or potent inhibitors of CYP2C8 hepatic enzymes.

• Receiving anticoagulant or antiplatelet therapy (such as aspirin>81mg/day, clopidogrel, warfarin).

• Contraindications to magnetic resonance imaging (MRI).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

Drug:
• Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral
• Placebo to match Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320007	Buenos Aires
Argentina	Investigational Site Number :0320001	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number :0320002	Capital Federal	Buenos Aires
Argentina	Investigational Site Number :0320006	Córdoba
Argentina	Investigational Site Number :0320005	San Miguel de Tucuman
Australia	Investigational Site Number :0360001	Fitzroy	Victoria
Australia	Investigational Site Number :0360006	Heidelberg West	Victoria
Australia	Investigational Site Number :0360004	Hobart	Tasmania
Australia	Investigational Site Number :0360002	Kent Town	South Australia
Australia	Investigational Site Number :0360003	Woolloongabba	Queensland
Austria	Investigational Site Number :0400003	Innsbruck
Austria	Investigational Site Number :0400001	Linz
Austria	Investigational Site Number :0400004	Linz
Austria	Investigational Site Number :0400002	Wien
Belarus	Investigational Site Number :1120004	Vitebsk
Belarus	Investigational Site Number :1120005	Vitebsk
Belgium	Investigational Site Number :0560007	Bruxelles
Belgium	Investigational Site Number :0560003	Edegem
Belgium	Investigational Site Number :0560006	Leuven
Belgium	Investigational Site Number :0560008	Liège
Belgium	Investigational Site Number :0560002	Mons
Belgium	Investigational Site Number :0560001	Pelt
Bulgaria	Investigational Site Number :1000002	Pleven
Bulgaria	Investigational Site Number :1000005	Plovdiv
Bulgaria	Investigational Site Number :1000001	Sofia
Bulgaria	Investigational Site Number :1000004	Sofia
Bulgaria	Investigational Site Number :1000006	Sofia
Bulgaria	Investigational Site Number :1000008	Sofia
Bulgaria	Investigational Site Number :1000009	Sofia
Canada	Investigational Site Number :1240017	Burnaby	British Columbia
Canada	Investigational Site Number :1240006	Gatineau	Quebec
Canada	Investigational Site Number :1240005	Greenfield Park	Quebec
Canada	Investigational Site Number :1240011	Halifax	Nova Scotia
Canada	Investigational Site Number :1240004	Montreal	Quebec
Canada	Investigational Site Number :1240015	Montreal	Quebec
Canada	Investigational Site Number :1240003	Ottawa	Ontario
Canada	Investigational Site Number :1240021	Quebec
Canada	Investigational Site Number :1240007	Sherbrooke	Quebec
Canada	Investigational Site Number :1240008	Toronto	Ontario
China	Investigational Site Number :1560003	Beijing
China	Investigational Site Number :1560006	Beijing
China	Investigational Site Number :1560009	Beijing
China	Investigational Site Number :1560012	Beijing
China	Investigational Site Number :1560021	Beijing
China	Investigational Site Number :1560004	Changchun
China	Investigational Site Number :1560015	Changsha
China	Investigational Site Number :1560005	Chengdu
China	Investigational Site Number :1560019	Chongqing
China	Investigational Site Number :1560035	Fuzhou
China	Investigational Site Number :1560001	Guangzhou
China	Investigational Site Number :1560007	Hangzhou
China	Investigational Site Number :1560014	Shijiazhuang
China	Investigational Site Number :1560008	Taiyuan
China	Investigational Site Number :1560017	Xi'an
Czechia	Investigational Site Number :2030002	Brno
Czechia	Investigational Site Number :2030004	Hradec Kralove
Czechia	Investigational Site Number :2030001	Jihlava
Czechia	Investigational Site Number :2030010	Ostrava - Poruba
Czechia	Investigational Site Number :2030005	Praha 2
Czechia	Investigational Site Number :2030003	Teplice
Denmark	Investigational Site Number :2080001	Esbjerg
Denmark	Investigational Site Number :2080005	Holstebro
Denmark	Investigational Site Number :2080004	Odense
Finland	Investigational Site Number :2460003	Helsinki
Finland	Investigational Site Number :2460001	Tampere
Finland	Investigational Site Number :2460002	Turku
France	Investigational Site Number :2500011	Bron
France	Investigational Site Number :2500005	Clermont Ferrand
France	Investigational Site Number :2500015	Gonesse
France	Investigational Site Number :2500009	Lille
France	Investigational Site Number :2500006	Montpellier
France	Investigational Site Number :2500008	Nancy
France	Investigational Site Number :2500010	Nantes
France	Investigational Site Number :2500017	Nimes
France	Investigational Site Number :2500007	Paris
France	Investigational Site Number :2500014	Paris
France	Investigational Site Number :2500016	Paris
France	Investigational Site Number :2500003	Rennes
France	Investigational Site Number :2500001	Strasbourg
France	Investigational Site Number :2500012	Toulouse
Germany	Investigational Site Number :2760005	Bayreuth
Germany	Investigational Site Number :2760009	Berlin
Germany	Investigational Site Number :2760001	Dresden
Germany	Investigational Site Number :2760012	Essen
Germany	Investigational Site Number :2760002	Gießen
Germany	Investigational Site Number :2760010	Halle (Saale)
Germany	Investigational Site Number :2760006	Hannover
Germany	Investigational Site Number :2760008	Münster
Germany	Investigational Site Number :2760004	Rostock
Germany	Investigational Site Number :2760011	Ulm
Greece	Investigational Site Number :3000001	Athens
Greece	Investigational Site Number :3000002	Athens
Greece	Investigational Site Number :3000006	Athens
Greece	Investigational Site Number :3000007	Athens
Greece	Investigational Site Number :3000004	Larissa
Greece	Investigational Site Number :3000003	Thessaloniki
Greece	Investigational Site Number :3000005	Thessaloniki
Hungary	Investigational Site Number :3480004	Budapest
Hungary	Investigational Site Number :3480007	Budapest
Hungary	Investigational Site Number :3480008	Budapest
Hungary	Investigational Site Number :3480002	Pécs
Hungary	Investigational Site Number :3480001	Szeged
Hungary	Investigational Site Number :3480006	Tatabánya
India	Investigational Site Number :3560003	Gurgaon
India	Investigational Site Number :3560007	Gurgaon
India	Investigational Site Number :3560005	India
India	Investigational Site Number :3560004	Mangaluru
India	Investigational Site Number :3560002	New Delhi
India	Investigational Site Number :3560006	New Delhi
Israel	Investigational Site Number :3760002	Ashkelon
Israel	Investigational Site Number :3760003	Haifa
Israel	Investigational Site Number :3760008	Jerusalem
Israel	Investigational Site Number :3760001	Tel HaShomer
Israel	Investigational Site Number :3760004	Zefat
Italy	Investigational Site Number :3800011	Bergamo
Italy	Investigational Site Number :3800007	Cagliari
Italy	Investigational Site Number :3800012	Firenze
Italy	Investigational Site Number :3800016	Firenze
Italy	Investigational Site Number :3800014	Genova
Italy	Investigational Site Number :3800013	L'Aquila
Italy	Investigational Site Number :3800001	Milano
Italy	Investigational Site Number :3800004	Milano
Italy	Investigational Site Number :3800010	Milano
Italy	Investigational Site Number :3800008	Pavia
Italy	Investigational Site Number :3800005	Roma
Italy	Investigational Site Number :3800009	Roma
Japan	Investigational Site Number :3920016	Chiba-shi	Chiba
Japan	Investigational Site Number :3920018	Kawagoe-shi	Saitama
Japan	Investigational Site Number :3920003	Kodaira-shi	Tokyo
Japan	Investigational Site Number :3920011	Kyoto-shi	Kyoto
Japan	Investigational Site Number :3920004	Moriguchi-shi	Osaka
Japan	Investigational Site Number :3920022	Morioka-shi	Iwate
Japan	Investigational Site Number :3920005	Niigata-shi	Niigata
Japan	Investigational Site Number :3920001	Osaka-shi	Osaka
Japan	Investigational Site Number :3920010	Ota-ku	Tokyo
Japan	Investigational Site Number :3920023	Sagamihara-shi
Japan	Investigational Site Number :3920020	Sendai-shi	Miyagi
Japan	Investigational Site Number :3920009	Ube-shi	Yamaguchi
Lithuania	Investigational Site Number :4400003	Kaunas
Lithuania	Investigational Site Number :4400002	Klaipeda
Lithuania	Investigational Site Number :4400001	Vilnius
Netherlands	Investigational Site Number :5280001	Amsterdam
Netherlands	Investigational Site Number :5280003	Breda
Netherlands	Investigational Site Number :5280006	Groningen
Netherlands	Investigational Site Number :5280002	Sittard-Geleen
Norway	Investigational Site Number :5780003	Bergen
Norway	Investigational Site Number :5780002	Namsos
Norway	Investigational Site Number :5780001	Oslo
Poland	Investigational Site Number :6160003	Bydgoszcz	Kujawsko-pomorskie
Poland	Investigational Site Number :6160002	Katowice	Slaskie
Poland	Investigational Site Number :6160004	Katowice	Slaskie
Poland	Investigational Site Number :6160007	Katowice	Slaskie
Poland	Investigational Site Number :6160001	Lodz
Poland	Investigational Site Number :6160012	Lublin
Poland	Investigational Site Number :6160008	Plewiska	Wielkopolskie
Poland	Investigational Site Number :6160005	Warszawa	Mazowieckie
Poland	Investigational Site Number :6160006	Warszawa	Mazowieckie
Poland	Investigational Site Number :6160011	Zabrze
Portugal	Investigational Site Number :6200001	Braga
Portugal	Investigational Site Number :6200006	Lisboa
Portugal	Investigational Site Number :6200007	Lisboa
Portugal	Investigational Site Number :6200011	Lisboa
Portugal	Investigational Site Number :6200002	Matosinhos
Portugal	Investigational Site Number :6200010	Porto
Romania	Investigational Site Number :6420008	Bucuresti
Romania	Investigational Site Number :6420004	Campulung
Romania	Investigational Site Number :6420006	Cluj-Napoca
Romania	Investigational Site Number :6420003	Constanta
Romania	Investigational Site Number :6420013	Oradea
Romania	Investigational Site Number :6420005	Sibiu
Romania	Investigational Site Number :6420001	Targu Mures
Romania	Investigational Site Number :6420002	Timisoara
Russian Federation	Investigational Site Number :6430018	Barnaul
Russian Federation	Investigational Site Number :6430023	Ekaterinburg
Russian Federation	Investigational Site Number :6430025	Kaliningrad
Russian Federation	Investigational Site Number :6430003	Kazan
Russian Federation	Investigational Site Number :6430022	Kemerovo
Russian Federation	Investigational Site Number :6430017	Kirov
Russian Federation	Investigational Site Number :6430024	Krasnoyarsk
Russian Federation	Investigational Site Number :6430001	Moscow
Russian Federation	Investigational Site Number :6430002	Moscow
Russian Federation	Investigational Site Number :6430008	Moscow
Russian Federation	Investigational Site Number :6430013	Moscow
Russian Federation	Investigational Site Number :6430020	Moscow
Russian Federation	Investigational Site Number :6430006	Nizhny Novgorod
Russian Federation	Investigational Site Number :6430021	Nizhny Novgorod
Russian Federation	Investigational Site Number :6430005	Novosibirsk
Russian Federation	Investigational Site Number :6430026	Perm
Russian Federation	Investigational Site Number :6430007	Pyatigorsk
Russian Federation	Investigational Site Number :6430016	Rostov-on-Don
Russian Federation	Investigational Site Number :6430004	Saint-Petersburg
Russian Federation	Investigational Site Number :6430009	Samara
Russian Federation	Investigational Site Number :6430019	Saransk
Russian Federation	Investigational Site Number :6430014	Smolensk
Russian Federation	Investigational Site Number :6430011	St-Petersburg
Russian Federation	Investigational Site Number :6430012	Tyumen
Russian Federation	Investigational Site Number :6430010	Ufa
Spain	Investigational Site Number :7240013	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240016	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240008	Córdoba
Spain	Investigational Site Number :7240012	Donostia	Pais Vasco
Spain	Investigational Site Number :7240017	Las Palmas de Gran Canaria	Las Palmas
Spain	Investigational Site Number :7240015	Lleida
Spain	Investigational Site Number :7240002	Madrid
Spain	Investigational Site Number :7240003	Madrid
Spain	Investigational Site Number :7240005	Madrid
Spain	Investigational Site Number :7240004	Majadahonda	Madrid
Spain	Investigational Site Number :7240009	Málaga
Spain	Investigational Site Number :7240010	Murcia
Spain	Investigational Site Number :7240001	Pozuelo De Alarcón	Madrid
Spain	Investigational Site Number :7240014	Salt	Girona [Gerona]
Spain	Investigational Site Number :7240007	Sevilla	Andalucia
Spain	Investigational Site Number :7240011	Valencia
Turkey	Investigational Site Number :7920005	Eskisehir
Turkey	Investigational Site Number :7920010	Hatay
Turkey	Investigational Site Number :7920002	Istanbul
Turkey	Investigational Site Number :7920003	Istanbul
Turkey	Investigational Site Number :7920006	Istanbul
Turkey	Investigational Site Number :7920007	Istanbul
Turkey	Investigational Site Number :7920009	Istanbul
Turkey	Investigational Site Number :7920013	Izmir
Turkey	Investigational Site Number :7920001	Izmit
Turkey	Investigational Site Number :7920011	Kütahya
Turkey	Investigational Site Number :7920012	Mersin
Turkey	Investigational Site Number :7920008	Trabzon
Ukraine	Investigational Site Number :8040008	Chernivtsi
Ukraine	Investigational Site Number :8040016	Chernivtsi
Ukraine	Investigational Site Number :8040003	Dnipro
Ukraine	Investigational Site Number :8040010	Ivano-Frankivsk
Ukraine	Investigational Site Number :8040007	Kharkiv
Ukraine	Investigational Site Number :8040011	Kharkiv
Ukraine	Investigational Site Number :8040012	Kharkiv
Ukraine	Investigational Site Number :8040013	Kyiv
Ukraine	Investigational Site Number :8040005	Lutsk
Ukraine	Investigational Site Number :8040004	Lviv
Ukraine	Investigational Site Number :8040009	Lviv
Ukraine	Investigational Site Number :8040002	Odesa
Ukraine	Investigational Site Number :8040006	Vinnytsia
Ukraine	Investigational Site Number :8040014	Zhytomyr
United Kingdom	Investigational Site Number :8260009	Bristol
United Kingdom	Investigational Site Number :8260001	Cardiff
United Kingdom	Investigational Site Number :8260003	Exeter	Devon
United Kingdom	Investigational Site Number :8260005	London
United Kingdom	Investigational Site Number :8260018	London
United Kingdom	Investigational Site Number :8260014	Newcastle Upon Tyne
United Kingdom	Investigational Site Number :8260012	Nottingham	Nottinghamshire
United Kingdom	Investigational Site Number :8260013	Oxford	Oxfordshire
United Kingdom	Investigational Site Number :8260008	Plymouth	Devon
United Kingdom	Investigational Site Number :8260019	Salford
United Kingdom	Investigational Site Number :8260010	Swansea	Neath Port Talbot
United States	University of New Mexico-Site Number:8400032	Albuquerque	New Mexico
United States	Arcadia Neurology Center-Site Number:8400070	Arcadia	California
United States	Mountain Neurological Research Center, Inc.-Site Number:8400128	Basalt	Colorado
United States	University of Alabama MS Center-Site Number:8400013	Birmingham	Alabama
United States	South Florida Neurology Associates-Site Number:8400029	Boca Raton	Florida
United States	Tufts Medical Center-Site Number:8400072	Boston	Massachusetts
United States	University Of Vermont College Of Medicine-Site Number:8400130	Burlington	Vermont
United States	Cleveland Clinic-Site Number:8400125	Cleveland	Ohio
United States	University Hospitals CMC-Site Number:8400083	Cleveland	Ohio
United States	Optimed Research, LTD-Site Number:8400147	Columbus	Ohio
United States	Neurology Clinic, PC-Site Number:8400087	Cordova	Tennessee
United States	Neurology Specialists-Site Number:8400002	Dayton	Ohio
United States	University of Colorado-Site Number:8400012	Denver	Colorado
United States	Wayne State University-Site Number:8400046	Detroit	Michigan
United States	Sanford Brain & Spine Center-Site Number:8400126	Fargo	North Dakota
United States	Advanced Neurosciences Research-Site Number:8400025	Fort Collins	Colorado
United States	Advanced Neuroscience Center-Site Number:8400035	Franklin	Tennessee
United States	Mountain View Clinical Research-Site Number:8400024	Greer	South Carolina
United States	Premier Neurology-Site Number:8400069	Greer	South Carolina
United States	Baylor College of Medicine-Site Number:8400136	Houston	Texas
United States	University of Kansas Medical Center-Site Number:8400023	Kansas City	Kansas
United States	UC San Diego ACTRI-Site Number:8400101	La Jolla	California
United States	Lou Ruvo Center for Brain Health-Site Number:8400117	Las Vegas	Nevada
United States	CHI Saint Joseph Medical Group Neurology-Site Number:8400110	Lexington	Kentucky
United States	Collaborative Neuroscience Research-Site Number:8400045	Long Beach	California
United States	Multiple Sclerosis Center-Site Number:8400143	Los Angeles	California
United States	Neurology Associates, PA-Site Number:8400004	Maitland	Florida
United States	Medical College of Wisconsin-Site Number:8400028	Milwaukee	Wisconsin
United States	Minneapolis Clinic of Neurology-Site Number:8400051	Minneapolis	Minnesota
United States	Aqualane Clinical Research-Site Number:8400027	Naples	Florida
United States	Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038	New York	New York
United States	Consultants In Neurology-Site Number:8400011	Northbrook	Illinois
United States	The Memorial Hospital-Site Number:8400033	Owosso	Michigan
United States	Jefferson Neurology Associates-Site Number:8400016	Philadelphia	Pennsylvania
United States	Perelman Center for Advanced Medicine-Site Number:8400142	Philadelphia	Pennsylvania
United States	Center for Neurology and Spine-Site Number:8400089	Phoenix	Arizona
United States	Providence Multiple Sclerosis Center-Site Number:8400020	Portland	Oregon
United States	Meridian Clinical Research, LLC-Site Number:8400005	Raleigh	North Carolina
United States	Mayo Clinic-Site Number:8400111	Rochester	Minnesota
United States	Missouri Baptist Medical Center-Site Number:8400019	Saint Louis	Missouri
United States	Neurology Center of San Antonio-Site Number:8400036	San Antonio	Texas
United States	University of San Francisco, Sandler Neurosciences Center-Site Number:8400137	San Francisco	California
United States	Meridian Clinical Research-Site Number:8400003	Savannah	Georgia
United States	Neurology Associates of Stony Brook-Site Number:8400042	Stony Brook	New York
United States	Axiom Clinical Research of Florida-Site Number:8400001	Tampa	Florida
United States	University of South Florida-Site Number:8400006	Tampa	Florida
United States	Holy Name Hospital-Site Number:8400104	Teaneck	New Jersey
United States	Harbor UCLA-Site Number:8400088	Torrance	California
United States	Regina Berkovich, MD, PhD-Site Number:8400059	West Hollywood	California
United States	Columbus Neuroscience-Site Number:8400010	Westerville	Ohio
United States	University of Massachusetts-Site Number:8400014	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Lithuania,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-month confirmed disability progression (CDP)	Time to onset of 6 months CDP defined as follows: -Increase of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.0, or -Increase of =0.5 point when the baseline EDSS score is >5.0 -	Up to 48 approximately months
Secondary	3-months change in T25-FW and 9-HPT	Time to onset of composite CDP, confirmed over at least 3 months (3-month CCDP), by the EDSS Plus composite (EDSS score increase, or 20% increase in the T25 FW test, or 20% increase in the 9 hole peg test (9 HPT)	Up to approximately 48 months
Secondary	3-month CDP	Time to onset of 3-month CDP as assessed by EDSS score	Up to approximately48 months
Secondary	New and enlarging T2 hyperintense lesions by MRI	Total number of new or enlarging T2 hyperintense lesions as detected by MRI	From Baseline up to approximately 48 months
Secondary	Time to onset of confirmed disability improvement (CDI)	Time to CDI defined as =1.0 point decrease on the EDSS score from baseline confirmed over at least 6 months	From Baseline up to approximately 48 months
Secondary	Brain volume loss (BVL)	Percent change in Brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6	From 6 Months up to approximately 48 months
Secondary	Change in cognitive function	Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) and by the California Verbal Learning Test (CVLT-II)	From Baseline up to approximately 48 months
Secondary	Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54)	Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS	From Baseline up to approximately 48 months
Secondary	Safety and Tolerability	Number of participants with adverse events (AEs), Serious AEs, AEs leading to permanent study intervention discontinuation, and adverse events of special interest (AESI)	From Screening until end of study up to approximately 48 months
Secondary	Population pharmacokinetics	Plasma concentration of SAR442168 and relevant metabolites (population PK assessment) at Months 6, 9, and 12	Months 6, 9 and 12
Secondary	Change in plasma neurofilament light chain (NfL)	Change in NfL levels at the EOS compared to baseline	From Baseline up to approximately 48 months
Secondary	Changes in serum Immunoglobulin level	Changes in serum Immunoglobulin level at the EOS compared to baseline	From Baseline up to approximately 48 months
Secondary	Change in lymphocyte phenotype subsets	Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants	From Baseline up to approximately 48 months
Secondary	Change in serum chitinase-3 like protein 1 (Chi3L1)	Change in serum chitinase-3 like protein 1 (Chi3L1) at the EOS compared to baseline	From Baseline up to approximately 48 months