Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2)

Relapsing Multiple Sclerosis Clinical Trial

— GEMINI 2  

Official title:

A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04410991
• Other study ID #: EFC16034
• Secondary ID: U1111-1238-13732
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 11, 2020
• Est. completion date: August 15, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS Secondary Objective: To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life To evaluate the safety and tolerability of daily SAR442168 To evaluate pharmacodynamics (PD) of SAR442168

Description:

Study duration will vary per participant in this event driven trial with a treatment duration of approximately 18 to 36 months. Participants completing the study will be offered to participate in a long term safety study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 900
• Est. completion date: August 15, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion criteria :

• The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent
• The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria
• The participant has an expanded disability status scale (EDSS) score =5.5 at the first Screening Visit
• The participant must have at least 1 of the following prior to screening:
• =1 documented relapse within the previous year OR
• =2 documented relapses within the previous 2 years, OR
• =1 documented Gd enhancing lesion on an MRI scan within the previous year
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Male participants are eligible to participate if they agree to the following during

the intervention period and until accelerated elimination procedure:

• Refrain from donating sperm

Plus either:

• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
• Must agree to use contraception/barrier as detailed below
• Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
• A female participant is eligible to participate if she is not pregnant or

breastfeeding, and at least one of the following conditions apply:

• Is not a WOCBP OR
• Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and until accelerated elimination procedure is completed (or for at least 10 days after the last dose of SAR442168, if the case was unblinded) and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for the same period of time.
• A WOCBP must have a negative highly sensitive pregnancy test at screening and within 24hours before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• The participant must have given written informed consent prior to undertaking any study related procedure. This includes consent to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where the legal age of maturity is greater than 18 years, a specific ICF for such legally minor participants must also be signed by the participant's legally authorized representative

Exclusion criteria:

• The participant has been diagnosed with primary progressive multiplesclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiplesclerosis (SPMS)
• The participant has a history of infection or may be at risk for infection including but not limited to: HIV, transplantation, live attenuated vaccines, progressive multifocal leukoencephalopathy, tuberculosis, hepatitis B or C, any persistent chronic or active recurring infection
• Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening.
• The participant has conditions or situations that would adversely affect participation

in this study, including but not limited to:

• A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist
• Medical condition(s) or concomitant disease(s) making them nonevaluable for the primary efficacy endpoint or that would adversely affect participation in this study, as judged by the Investigator
• A requirement for concomitant treatment that could bias the primary evaluation
• The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study
• At screening, the participant is positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or is positive for hepatitis C antibody
• The participant has any of the following:
• 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
• The participant has a lymphocyte count below the lower limit of normal (LLN) at the screening visit
• The presence of psychiatric disturbance or substance abuse
• Prior/concomitant therapy
• The participant is receiving potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes
• The participant is receiving anticoagulant/antiplatelet therapies
• 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
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Tolebrutinib
Pharmaceutical form: Tablet Route of administration: Oral
• Teriflunomide HMR1726
Pharmaceutical form: Tablet Route of administration: Oral
• Placebo to match Tolebrutinib
Pharmaceutical form: Tablet Route of administration: Oral
• Placebo to match Teriflunomide
Pharmaceutical form: Tablet Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320001	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number :0320004	Caba	Buenos Aires
Argentina	Investigational Site Number :0320002	Capital Federal	Buenos Aires
Argentina	Investigational Site Number :0320003	Rosario	Santa Fe
Argentina	Investigational Site Number :0320005	San Miguel de Tucuman
Belgium	Investigational Site Number :0560005	Brugge
Belgium	Investigational Site Number :0560004	Gent
Belgium	Investigational Site Number :0560002	Mons
Belgium	Investigational Site Number :0560001	Pelt
Brazil	Investigational Site Number :0760002	Curitiba
Brazil	Investigational Site Number :0760001	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760007	Sao Paulo
Canada	Investigational Site Number :1240002	Edmonton	Alberta
Canada	Investigational Site Number :1240006	Gatineau
Canada	Investigational Site Number :1240005	Greenfield Park	Quebec
Canada	Investigational Site Number : 1240012	Hamilton	Ontario
Canada	Investigational Site Number :1240014	London	Ontario
Canada	Investigational Site Number :1240021	Quebec
Chile	Investigational Site Number :1520006	Concepción
Chile	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520004	Valdivia
Croatia	Investigational Site Number :1910001	Zagreb
Croatia	Investigational Site Number :1910002	Zagreb
Croatia	Investigational Site Number :1910003	Zagreb
Czechia	Investigational Site Number :2030002	Brno
Czechia	Investigational Site Number :2030011	Hradec Kralove
Czechia	Investigational Site Number :2030001	Jihlava
Czechia	Investigational Site Number :2030008	Praha 10
Czechia	Investigational Site Number :2030005	Praha 5 - Motol
France	Investigational Site Number :2500019	Besancon
France	Investigational Site Number :2500018	Bordeaux
France	Investigational Site Number :2500011	Bron
France	Investigational Site Number :2500005	Clermont Ferrand
France	Investigational Site Number :2500006	Montpellier
France	Investigational Site Number :2500010	Nantes
France	Investigational Site Number :2500002	Nice
France	Investigational Site Number :2500017	Nimes
France	Investigational Site Number :2500007	Paris
France	Investigational Site Number :2500004	Poissy
France	Investigational Site Number :2500003	Rennes
France	Investigational Site Number :2500001	Strasbourg
Germany	Investigational Site Number :2760005	Bayreuth
Germany	Investigational Site Number :2760014	Berlin
Germany	Investigational Site Number :2760015	Berlin
Germany	Investigational Site Number :2760020	Bochum
Germany	Investigational Site Number :2760012	Essen
Germany	Investigational Site Number :2760003	Würzburg
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 :3000009	Athens
Greece	Investigational Site Number :3000004	Larissa
Greece	Investigational Site Number :3000003	Thessaloniki
Hungary	Investigational Site Number :3480102	Budapest
Hungary	Investigational Site Number :3480105	Budapest
Hungary	Investigational Site Number :3480106	Kaposvár
Hungary	Investigational Site Number :3480103	Tatabánya
India	Investigational Site Number :3560005	Chandigarh
India	Investigational Site Number :3560007	Gurgaon
India	Investigational Site Number :3560008	Gurgaon
India	Investigational Site Number :3560002	New Delhi
India	Investigational Site Number :3560004	Thiruvananthapuram
Israel	Investigational Site Number :3760002	Ashkelon
Israel	Investigational Site Number :3760003	Haifa
Israel	Investigational Site Number :3760006	Rehovot
Israel	Investigational Site Number :3760004	Safed
Israel	Investigational Site Number :3760001	Tel HaShomer
Korea, Republic of	Investigational Site Number :4100001	Goyang-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100006	Seoul	Seoul-teukbyeolsi
Latvia	Investigational Site Number :4280002	Riga
Latvia	Investigational Site Number :4280003	Riga
Netherlands	Investigational Site Number :5280001	Amsterdam
Norway	Investigational Site Number :5780002	Namsos
Norway	Investigational Site Number :5780001	Oslo
Portugal	Investigational Site Number :6200001	Braga
Portugal	Investigational Site Number :6200005	Coimbra
Portugal	Investigational Site Number :6200006	Lisboa
Portugal	Investigational Site Number :6200011	Lisboa
Portugal	Investigational Site Number :6200002	Matosinhos
Portugal	Investigational Site Number :6200010	Porto
Portugal	Investigational Site Number :6200004	Santa Maria da Feira
Puerto Rico	San Juan MS Center-Site Number:8400015	Guaynabo
Russian Federation	Investigational Site Number :6430006	Barnaul
Russian Federation	Investigational Site Number :6430013	Bryansk
Russian Federation	Investigational Site Number :6430012	Ekaterinburg
Russian Federation	Investigational Site Number :6430001	Kazan
Russian Federation	Investigational Site Number :6430010	Kirov
Russian Federation	Investigational Site Number :6430005	Moscow
Russian Federation	Investigational Site Number :6430007	Moscow
Russian Federation	Investigational Site Number :6430003	Novosibirsk
Russian Federation	Investigational Site Number :6430002	Saint-Petersburg
Russian Federation	Investigational Site Number :6430014	Saint-Petersburg
Russian Federation	Investigational Site Number :6430011	Saransk
Russian Federation	Investigational Site Number :6430004	St-Petersburg
Serbia	Investigational Site Number :6880001	Belgrade
Serbia	Investigational Site Number :6880003	Belgrade
Serbia	Investigational Site Number :6880006	Belgrade
Serbia	Investigational Site Number :6880002	Kragujevac
Serbia	Investigational Site Number :6880004	Nis
Serbia	Investigational Site Number :6880005	Novi Sad
Slovakia	Investigational Site Number :7030001	Bratislava
Slovakia	Investigational Site Number :7030002	Martin
Slovakia	Investigational Site Number :7030004	Nitra
Spain	Investigational Site Number :7240009	Barakaldo	Bizkaia
Spain	Investigational Site Number :7240006	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240007	Hospitalet de Llobregat
Spain	Investigational Site Number :7240008	La Coruña
Spain	Investigational Site Number :7240013	Las Palmas de Gran Canaria	Las Palmas
Spain	Investigational Site Number :7240005	Lleida
Spain	Investigational Site Number :7240001	Madrid
Spain	Investigational Site Number :7240002	Madrid
Spain	Investigational Site Number :7240003	Madrid
Spain	Investigational Site Number :7240010	Málaga
Spain	Investigational Site Number :7240012	Pozuelo De Alarcón
Spain	Investigational Site Number :7240004	Salt	Girona [Gerona]
Spain	Investigational Site Number :7240011	Sevilla	Andalucia
Switzerland	Investigational Site Number :7560003	Aarau
Switzerland	Investigational Site Number :7560002	Bern
Switzerland	Investigational Site Number :7560004	Lugano
Turkey	Investigational Site Number :7920002	Ankara
Turkey	Investigational Site Number :7920005	Besevler / Ankara
Turkey	Investigational Site Number :7920006	Istanbul
Turkey	Investigational Site Number :7920004	Kuttahta
Turkey	Investigational Site Number :7920001	Samsun
Turkey	Investigational Site Number :7920003	Trabzon
Ukraine	Investigational Site Number :8040020	Chernihiv
Ukraine	Investigational Site Number :8040002	Chernivtsi
Ukraine	Investigational Site Number :8040019	Chernivtsi
Ukraine	Investigational Site Number :8040005	Dnipro
Ukraine	Investigational Site Number :8040018	Kharkiv
Ukraine	Investigational Site Number :8040022	Kharkiv
Ukraine	Investigational Site Number :8040007	Kyiv
Ukraine	Investigational Site Number :8040006	Lviv
Ukraine	Investigational Site Number :8040003	Vinnytsia
United Kingdom	Investigational Site Number :8260009	Bristol
United Kingdom	Investigational Site Number :8260016	Canterbury	Kent
United Kingdom	Investigational Site Number :8260003	Exeter	Devon
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	The NeuroMedical Center-Site Number:8400057	Baton Rouge	Louisiana
United States	South Florida Neurology Associates-Site Number:8400029	Boca Raton	Florida
United States	Dayton Center for Neurological Disorders-Site Number:8400081	Centerville	Ohio
United States	Novant Health Multiple Sclerosis Care Center - South Park-Site Number:8400120	Charlotte	North Carolina
United States	North Central Neurology Associates, PC-Site Number:8400009	Cullman	Alabama
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	Fort Wayne Neurological Center-Site Number:8400039	Fort Wayne	Indiana
United States	Advanced Neuroscience Center-Site Number:8400035	Franklin	Tennessee
United States	University of Florida Health-Site Number:8400159	Gainesville	Florida
United States	Premier Neurology-Site Number:8400069	Greer	South Carolina
United States	Hackensack University Hospital-Site Number:8400047	Hackensack	New Jersey
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	Sibyl Wray, MD, Neurology, PC-Site Number:8400007	Knoxville	Tennessee
United States	CHI Saint Joseph Medical Group Neurology-Site Number:8400110	Lexington	Kentucky
United States	University of Kentucky-Site Number:8400106	Lexington	Kentucky
United States	Norton Neurology MS Services-Site Number:8400127	Louisville	Kentucky
United States	International Neurorehabilitation Institute-Site Number:8400034	Lutherville-Timonium	Maryland
United States	Neurology Associates, PA-Site Number:8400004	Maitland	Florida
United States	University of Miami-Site Number:8400063	Miami	Florida
United States	Wheaton Franciscan Healthcare-Site Number:8400022	Milwaukee	Wisconsin
United States	Minneapolis Clinic of Neurology-Site Number:8400051	Minneapolis	Minnesota
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	West Omaha Family Physicians-Site Number:8400139	Omaha	Nebraska
United States	South Shore Neurologic Associates-Site Number:8400100	Patchogue	New York
United States	Jefferson Neurology Associates-Site Number:8400016	Philadelphia	Pennsylvania
United States	Center for Neurology and Spine-Site Number:8400089	Phoenix	Arizona
United States	Meridian Clinical Research, LLC-Site Number:8400005	Raleigh	North Carolina
United States	Neurological Associates-Site Number:8400097	Richmond	Virginia
United States	Neurology Center of San Antonio-Site Number:8400036	San Antonio	Texas
United States	Meridian Clinical Research-Site Number:8400003	Savannah	Georgia
United States	Texas Institute for Neuroogical Disorders-Sherman-Site Number:8400151	Sherman	Texas
United States	Prairie Education and Research Cooperative-Site Number:8400071	Springfield	Illinois
United States	Infinity Clinical Research-Site Number:8400008	Sunrise	Florida
United States	University of South Florida-Site Number:8400006	Tampa	Florida
United States	Harbor UCLA-Site Number:8400088	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  Croatia,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Korea, Republic of,  Latvia,  Netherlands,  Norway,  Portugal,  Puerto Rico,  Russian Federation,  Serbia,  Slovakia,  Spain,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses	Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses	Up to approximately 36 months
Secondary	Time to onset of confirmed disability worsening confirmed over at least 6 months	ime to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as follows: increase of =1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0 OR; increase of =1.0 point from the baseline EDSS score when the baseline score is 0.5 to =5.5 OR; increase of =0.5 point from the baseline EDSS score when the baseline score is >5.5 - 5.	Up to approximately 36 months
Secondary	Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months		Up to 36 approximately months
Secondary	Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study		From 6 months up to approximately 36 months
Secondary	Total Number of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the End of study (EOS)		From 6 months up to approximately 36 months
Secondary	Change in cognitive function	Change in cognitive function from baseline to the EOS as assessed by the SDMT and CVLT-II where available	From Baseline up to 36 approximately months
Secondary	Time to confirmed disability improvement	Time to confirmed disability improvement (CDI), defined as a =1.0 point decrease on the EDSS from the baseline EDSS score confirmed over at least 6 months	From Baseline up to approximately 36 months
Secondary	Percent change in Brain volume Loss as detected by brain MRI	Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS	From 6 months up to approximately 36 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 36 months
Secondary	Number of participants with adverse events A(Es) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI)		From screening until end of study approximately 36 months
Secondary	Change in plasma neurofilament light chain (NfL)	Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baselineC	From Baseline until end of study up to approximately 36 months -
Secondary	Changes in plasma Immunoglobulin level	Changes in serum immunoglobulin level at the EOS compared to baseline	From Baseline until end of study up to 36 approximately months
Secondary	Change in serum chitinase-3 like protein 1 (Chi3L1) -	Change in serum Chi3L1 levels at the EOS compared to baseline -	From Baseline until end of study up to approximately 36 months -