Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS)

Primary Progressive Multiple Sclerosis Clinical Trial

— PERSEUS  

Official title:

A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Primary Progressive Multiple Sclerosis (PERSEUS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04458051
• Other study ID #: EFC16035
• Secondary ID: U1111-1238-13182
• Status: Recruiting
• Phase: Phase 3
• Start date: August 13, 2020
• Est. completion date: July 25, 2025

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• 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 primary progressive multiple sclerosis (PPMS)

Secondary Objectives:

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 in PPMS and its relationship to efficacy and safety To evaluate pharmacodynamics of SAR442168

Description:

Study duration will vary per participant in this event driven trial with a treatment duration of approximately 12 to 60 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: July 25, 2025
• Est. primary completion date: July 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria: - 18 to 55 years of age inclusive

• Diagnosis of PPMS according to the 2017 McDonald criteria

• Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at screening inclusive

• Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history.

• Contraceptive use consistent with local regulations for individuals participating in clinical studies

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

• Is not a woman of childbearing potential (WOCBP) or is a WOCBP and agrees to use an acceptable contraceptive method

• the participant must not have access to ocrelizumab (eg, ocrelizumab not available on the national market or not reimbursed for the approved indication).

• the participant must have access to and be eligible to be treated with ocrelizumab but: 1) does not tolerate it due to side effects or safety reasons; and/or 2) has failed ocrelizumab treatment due to perceived lack of efficacy Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:

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

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

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

• History of malignancy within 5 years prior to screening.

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

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

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

• A bleeding disorder or known platelet dysfunction at any time prior to the screening visit.

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

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

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

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

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

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

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

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

• Contraindications to magnetic resonance imaging (MRI). NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Primary Progressive Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Tolebrutinib
Pharmaceutical form: Film-coated Tablet Route of administration: Oral
• Placebo
Pharmaceutical form: Film-coated Tablet Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320004	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320003	Rosario	Santa Fe
Australia	Investigational Site Number : 0360005	Concord	New South Wales
Australia	Investigational Site Number : 0360003	Hobart	Tasmania
Australia	Investigational Site Number : 0360006	St Leonards	New South Wales
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 : 0560009	Bruxelles
Belgium	Investigational Site Number : 0560003	Edegem
Belgium	Investigational Site Number : 0560004	Gent
Belgium	Investigational Site Number : 0560006	Leuven
Belgium	Investigational Site Number : 0560008	Liège
Belgium	Investigational Site Number : 0560002	Mons
Belgium	Investigational Site Number : 0560001	Pelt
Belgium	Investigational Site Number : 0560007	Sint-Lambrechts-Woluwe
Bulgaria	Investigational Site Number : 1000002	Pleven
Bulgaria	Investigational Site Number : 1000001	Sofia
Bulgaria	Investigational Site Number : 1000004	Sofia
Bulgaria	Investigational Site Number : 1000008	Sofia
Bulgaria	Investigational Site Number : 1000011	Sofia
Canada	Investigational Site Number : 1240002	Edmonton	Alberta
Canada	Investigational Site Number : 1240012	Hamilton	Ontario
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 : 1240001	Quebec
Canada	Investigational Site Number : 1240021	Quebec
Canada	Investigational Site Number : 1240007	Sherbrooke	Quebec
Canada	Investigational Site Number : 1240013	Toronto	Ontario
Chile	Investigational Site Number : 1520006	Concepcion	Biobío
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
China	Investigational Site Number : 1560003	Beijing
China	Investigational Site Number : 1560009	Beijing
China	Investigational Site Number : 1560012	Beijing
China	Investigational Site Number : 1560021	Beijing
China	Investigational Site Number : 1560025	Beijing
China	Investigational Site Number : 1560004	Changchun
China	Investigational Site Number : 1560015	Changsha
China	Investigational Site Number : 1560005	Chengdu
China	Investigational Site Number : 1560035	Fuzhou
China	Investigational Site Number : 1560002	Guangzhou
China	Investigational Site Number : 1560027	Hohhot
China	Investigational Site Number : 1560001	Shanghai
China	Investigational Site Number : 1560008	Taiyuan
China	Investigational Site Number : 1560020	Tianjin
China	Investigational Site Number : 1560026	Wenzhou
Colombia	Investigational Site Number : 1700001	Bogota
Colombia	Investigational Site Number : 1700003	Bogotá
Croatia	Investigational Site Number : 1910001	Zagreb
Croatia	Investigational Site Number : 1910002	Zagreb
Czechia	Investigational Site Number : 2030002	Brno
Czechia	Investigational Site Number : 2030004	Hradec Kralove
Czechia	Investigational Site Number : 2030001	Jihlava
Czechia	Investigational Site Number : 2030003	Teplice
Denmark	Investigational Site Number : 2080001	Esbjerg
Denmark	Investigational Site Number : 2080005	Holstebro
Estonia	Investigational Site Number : 2330001	Tallinn
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 : 2500017	Nimes
France	Investigational Site Number : 2500007	Paris
France	Investigational Site Number : 2500014	Paris
France	Investigational Site Number : 2500004	Poissy
France	Investigational Site Number : 2500003	Rennes
France	Investigational Site Number : 2500001	Strasbourg
France	Investigational Site Number : 2500012	Toulouse
Georgia	Investigational Site Number : 2680003	Tbilisi
Georgia	Investigational Site Number : 2680004	Tbilisi
Georgia	Investigational Site Number : 2680005	Tbilisi
Georgia	Investigational Site Number : 2680006	Tbilisi
Georgia	Investigational Site Number : 2680009	Tbilisi
Germany	Investigational Site Number : 2760005	Bayreuth
Germany	Investigational Site Number : 2760009	Berlin
Germany	Investigational Site Number : 2760015	Berlin
Germany	Investigational Site Number : 2760020	Bochum
Germany	Investigational Site Number : 2760001	Dresden
Germany	Investigational Site Number : 2760021	Düsseldorf
Germany	Investigational Site Number : 2760012	Essen
Germany	Investigational Site Number : 2760002	Gießen
Germany	Investigational Site Number : 2760006	Hannover
Germany	Investigational Site Number : 2760018	München
Germany	Investigational Site Number : 2760008	Münster
Germany	Investigational Site Number : 2760004	Rostock
Germany	Investigational Site Number : 2760011	Ulm
Greece	Investigational Site Number : 3000001	Athens
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number : 3000006	Athens
Greece	Investigational Site Number : 3000004	Larissa
Greece	Investigational Site Number : 3000007	Maroussi
Greece	Investigational Site Number : 3000003	Thessaloniki
Greece	Investigational Site Number : 3000009	Thessaloniki
Hungary	Investigational Site Number : 3480202	Budapest
Hungary	Investigational Site Number : 3480203	Budapest
Hungary	Investigational Site Number : 3480205	Budapest
Hungary	Investigational Site Number : 3480204	Kistarcsa
India	Investigational Site Number : 3560014	Bengaluru
India	Investigational Site Number : 3560003	Gurgaon
India	Investigational Site Number : 3560007	Gurgaon
India	Investigational Site Number : 3560004	Mangaluru
India	Investigational Site Number : 3560002	New Delhi
India	Investigational Site Number : 3560005	New Delhi
Israel	Investigational Site Number : 3760008	Jerusalem
Israel	Investigational Site Number : 3760001	Ramat Gan
Israel	Investigational Site Number : 3760004	Safed
Italy	Investigational Site Number : 3800007	Cagliari
Italy	Investigational Site Number : 3800015	Catania
Italy	Investigational Site Number : 3800018	Chieti
Italy	Investigational Site Number : 3800016	Firenze
Italy	Investigational Site Number : 3800001	Milano
Italy	Investigational Site Number : 3800003	Napoli
Italy	Investigational Site Number : 3800006	Napoli
Italy	Investigational Site Number : 3800002	Pozzilli	Isernia
Italy	Investigational Site Number : 3800013	Roma
Japan	Investigational Site Number : 3920014	Bunkyo-ku	Tokyo
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 : 3920008	Koriyama-shi	Fukushima
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	Kanagawa
Japan	Investigational Site Number : 3920020	Sendai-shi	Miyagi
Japan	Investigational Site Number : 3920017	Shinjuku-ku	Tokyo
Japan	Investigational Site Number : 3920015	Toyama-shi	Toyama
Latvia	Investigational Site Number : 4280002	Riga
Latvia	Investigational Site Number : 4280003	Riga
Mexico	Investigational Site Number : 4840004	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840001	Mexico city
Mexico	Investigational Site Number : 4840005	Mexico city
Mexico	Investigational Site Number : 4840007	Tlalnepantla
Mexico	Investigational Site Number : 4840003	Veracruz
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 : 5780005	Tromsø
Peru	Investigational Site Number : 6040004	Lima
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	Lódzkie
Poland	Investigational Site Number : 6160005	Warszawa	Mazowieckie
Poland	Investigational Site Number : 6160006	Warszawa	Mazowieckie
Portugal	Investigational Site Number : 6200001	Braga
Portugal	Investigational Site Number : 6200016	Leiria
Portugal	Investigational Site Number : 6200007	Lisboa
Portugal	Investigational Site Number : 6200012	Lisboa
Portugal	Investigational Site Number : 6200002	Matosinhos
Portugal	Investigational Site Number : 6200010	Porto
Portugal	Investigational Site Number : 6200004	Santa Maria da Feira
Romania	Investigational Site Number : 6420008	Bucuresti
Romania	Investigational Site Number : 6420004	Campulung
Romania	Investigational Site Number : 6420003	Constanta
Romania	Investigational Site Number : 6420013	Oradea
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 : 6430022	Ekaterinburg
Russian Federation	Investigational Site Number : 6430023	Kaliningrad
Russian Federation	Investigational Site Number : 6430004	Kazan
Russian Federation	Investigational Site Number : 6430021	Krasnoyarsk
Russian Federation	Investigational Site Number : 6430011	Moscow
Russian Federation	Investigational Site Number : 6430013	Moscow
Russian Federation	Investigational Site Number : 6430014	Nizhny Novgorod
Russian Federation	Investigational Site Number : 6430008	Pyatigorsk
Russian Federation	Investigational Site Number : 6430015	Rostov-on-Don
Russian Federation	Investigational Site Number : 6430017	Saint-Petersburg
Russian Federation	Investigational Site Number : 6430009	Samara
Russian Federation	Investigational Site Number : 6430020	Saransk
Russian Federation	Investigational Site Number : 6430007	Tyumen
Russian Federation	Investigational Site Number : 6430006	Ufa
Serbia	Investigational Site Number : 6880001	Belgrade
Serbia	Investigational Site Number : 6880002	Kragujevac
Serbia	Investigational Site Number : 6880004	Nis
Singapore	Investigational Site Number : 7020002	Singapore
South Africa	Investigational Site Number : 7100001	Pretoria
Spain	Investigational Site Number : 7240010	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240013	Bilbao	Bizkaia
Spain	Investigational Site Number : 7240004	Córdoba
Spain	Investigational Site Number : 7240012	La Coruña	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240016	Las Palmas de Gran Canaria	Las Palmas
Spain	Investigational Site Number : 7240003	Madrid
Spain	Investigational Site Number : 7240002	Majadahonda	Madrid
Spain	Investigational Site Number : 7240005	Malaga
Spain	Investigational Site Number : 7240006	Murcia
Spain	Investigational Site Number : 7240014	Palma de Mallorca
Spain	Investigational Site Number : 7240001	Pozuelo De Alarcón	Madrid
Spain	Investigational Site Number : 7240011	Salt	Girona [Gerona]
Spain	Investigational Site Number : 7240015	Santiago de Compostela	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240007	Sevilla	Andalucia
Spain	Investigational Site Number : 7240008	Valencia
Sweden	Investigational Site Number : 7520001	Göteborg
Sweden	Investigational Site Number : 7520005	Motala
Turkey	Investigational Site Number : 7920009	Ankara
Turkey	Investigational Site Number : 7920014	Ankara
Turkey	Investigational Site Number : 7920005	Eskisehir
Turkey	Investigational Site Number : 7920010	Hatay
Turkey	Investigational Site Number : 7920002	Istanbul
Turkey	Investigational Site Number : 7920003	Istanbul
Turkey	Investigational Site Number : 7920007	Istanbul
Turkey	Investigational Site Number : 7920016	Istanbul
Turkey	Investigational Site Number : 7920015	Izmir
Turkey	Investigational Site Number : 7920001	Izmit
Turkey	Investigational Site Number : 7920011	Kutahya
Turkey	Investigational Site Number : 7920012	Mersin
Turkey	Investigational Site Number : 7920013	Samsun
Ukraine	Investigational Site Number : 8040020	Chernivtsi
Ukraine	Investigational Site Number : 8040012	Ivano-Frankivsk
Ukraine	Investigational Site Number : 8040017	Kharkiv
Ukraine	Investigational Site Number : 8040023	Kharkiv
Ukraine	Investigational Site Number : 8040025	Kharkiv
Ukraine	Investigational Site Number : 8040013	Kyiv
Ukraine	Investigational Site Number : 8040014	Kyiv
Ukraine	Investigational Site Number : 8040015	Kyiv
Ukraine	Investigational Site Number : 8040011	Lutsk
Ukraine	Investigational Site Number : 8040002	Lviv
Ukraine	Investigational Site Number : 8040007	Lviv
Ukraine	Investigational Site Number : 8040010	Odesa
Ukraine	Investigational Site Number : 8040024	Vinnytsya
Ukraine	Investigational Site Number : 8040008	Zhytormyr
United Kingdom	Investigational Site Number : 8260009	Bristol
United Kingdom	Investigational Site Number : 8260016	Canterbury	Kent
United Kingdom	Investigational Site Number : 8260001	Cardiff	Vale Of Glamorgan, The
United Kingdom	Investigational Site Number : 8260005	London	London, City Of
United Kingdom	Investigational Site Number : 8260006	London	London, City Of
United Kingdom	Investigational Site Number : 8260012	Nottingham	Nottinghamshire
United Kingdom	Investigational Site Number : 8260013	Oxford	Oxfordshire
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	South Florida Neurology Associates Site Number : 8400029	Boca Raton	Florida
United States	Tufts Medical Center Site Number : 8400072	Boston	Massachusetts
United States	Novant Health Multiple Sclerosis Care Center - South Park Site Number : 8400120	Charlotte	North Carolina
United States	Cleveland Clinic Site Number : 8400125	Cleveland	Ohio
United States	The Boster Center for Multiple Sclerosis Site Number : 8400147	Columbus	Ohio
United States	The Ohio State University Wexner Medical Center Site Number : 8400150	Columbus	Ohio
United States	University of Colorado Site Number : 8400012	Denver	Colorado
United States	Wayne State University Site Number : 8400046	Detroit	Michigan
United States	Duke Neurological Disorders Clinic Site Number : 8400098	Durham	North Carolina
United States	Michigan Institute For Neurological Disorders Site Number : 8400058	Farmington Hills	Michigan
United States	Advanced Neurosciences Research Site Number : 8400025	Fort Collins	Colorado
United States	Advanced Neuroscience Center Site Number : 8400035	Franklin	Tennessee
United States	University of Florida, Fixel Center for Neurology Site Number : 8400159	Gainesville	Florida
United States	Mountain View Clinical Research Site Number : 8400024	Greer	South Carolina
United States	Hackensack University Hospital Site Number : 8400047	Hackensack	New Jersey
United States	Hawaii Pacific Neuroscience Site Number : 8400103	Honolulu	Hawaii
United States	Saint Luke's Hospital Site Number : 8400153	Kansas City	Missouri
United States	Mt Olympus Medical Research Site Number : 8400163	Katy	Texas
United States	UC San Diego ACTRI Site Number : 8400101	La Jolla	California
United States	University of Kentucky Site Number : 8400106	Lexington	Kentucky
United States	Collaborative Neuroscience Research Site Number : 8400045	Los Alamitos	California
United States	Multiple Sclerosis Center Site Number : 8400143	Los Angeles	California
United States	International Neurorehabilitation Institute Site Number : 8400034	Lutherville	Maryland
United States	Neurology Associates, PA Site Number : 8400004	Maitland	Florida
United States	Methodist Hospital Site Number : 8400164	Merrillville	Indiana
United States	Medical College of Wisconsin Site Number : 8400028	Milwaukee	Wisconsin
United States	Wheaton Franciscan Healthcare Site Number : 8400022	Milwaukee	Wisconsin
United States	Ochsner Baptist Clinical Trials Unit (CTU) Site Number : 8400107	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai (Department of Endoc Site Number : 8400038	New York	New York
United States	Multiple Sclerosis Center of California Site Number : 8400135	Newport Beach	California
United States	Consultants In Neurology Site Number : 8400011	Northbrook	Illinois
United States	University Of Nebraska Site Number : 8400129	Omaha	Nebraska
United States	College Park Family Care Center Site Number : 8400044	Overland Park	Kansas
United States	The Memorial Hospital Site Number : 8400033	Owosso	Michigan
United States	Sharlin Health & Neurology Site Number : 8400093	Ozark	Missouri
United States	SC3 Research - Pasadena Site Number : 8400070	Pasadena	California
United States	Jefferson Neurology Associates Site Number : 8400016	Philadelphia	Pennsylvania
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	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	Velocity Clinical Research Site Number : 8400003	Savannah	Georgia
United States	Prairie Education and Research Cooperative Site Number : 8400071	Springfield	Illinois
United States	Neurology Associates of Stony Brook Site Number : 8400042	Stony Brook	New York
United States	University of South Florida Site Number : 8400006	Tampa	Florida
United States	Harbor UCLA Site Number : 8400088	Torrance	California
United States	Atrium Health Wake Forest Baptist Site Number : 8400116	Winston-Salem	North Carolina
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,  Chile,  China,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Georgia,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Latvia,  Mexico,  Netherlands,  Norway,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  South Africa,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-month composite Confirmed Disability Progression (cCDP)	Time to onset of 3-month cCDP defined as follows: Increase over at least 3 months of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.5, or =0.5 points when the baseline EDSS score is >5.5, or =20% from the baseline T25-FW, or =20% from the baseline 9-HPT	Up to approximately 60 months
Secondary	6-month Confirmed Disability Progression (CDP)	Time to onset of 6-month CDP as assessed by EDSS score	Up to approximately 60 months
Secondary	6-month composite Confirmed Disability Progression (cCDP)	Time to onset of 6-month cCDP	Up to approximately 60 months
Secondary	Change in T2 hyperintense lesions by MRI	Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI after baseline up to and including the end of study (EOS)	From screening MRI to approximately 60 months
Secondary	Time to onset of confirmed disability improvement (CDI)	Time to onset of CDI defined as =1.0-point decrease on the EDSS score from baseline confirmed over at least 6 months	Up to approximately 60 months
Secondary	Percent change in Brain volume (BV)	Percent change in brain volume (BV) as detected by brain MRI at the EOS compared to month 6	From 6 months up to approximately 60 months
Secondary	Change in cognitive function as assessed by SDMT	Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT)	From Baseline up to approximately 60 months
Secondary	Change in cognitive function as assessed by CVLT-II	Change in cognitive function at the EOS compared to baseline as assessed by the California Verbal Learning Test II (CVLT-II) where available	From Baseline up to approximately 60 months
Secondary	Change in Multiple Sclerosis Quality of Life	Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) at the EOS compared to baseline	From Baseline up to approximately 60 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 up to approximately 60 months
Secondary	Population pharmacokinetics	Plasma concentration of SAR442168 (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 from at the EOS compared to baseline	From Baseline up to approximately 60 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 60 months
Secondary	Changes in serum Immunoglobulin level	Changes in serum Immunoglobulin level at the EOS compared to baseline	From Baseline up to approximately 60 months
Secondary	Change in serum chitinase-3 like protein 1 (Chi3L1)	Change in serum Chi3L1 at EOS compared to baseline	From Baseline up to approximately 60 months