Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2)
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Drug: Placebo to match Tolebrutinib
- Registration Number
- NCT04410991
- Lead Sponsor
- Sanofi
- Brief 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
- Detailed 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 900
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Teriflunomide Teriflunomide HMR1726 Oral 14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily SAR442168 Placebo to match Teriflunomide Dose 1 of oral SAR442168 daily + placebo to match the teriflunomide tablet once daily Teriflunomide Placebo to match Tolebrutinib Oral 14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily SAR442168 Tolebrutinib Dose 1 of oral SAR442168 daily + placebo to match the teriflunomide tablet once daily
- Primary Outcome Measures
Name Time Method Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses Up to approximately 36 months Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses
- Secondary Outcome Measures
Name Time Method Time to confirmed disability improvement From Baseline up to approximately 36 months 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
Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months Up to 36 approximately months Time to onset of confirmed disability worsening confirmed over at least 6 months Up to approximately 36 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.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 Percent change in Brain volume Loss as detected by brain MRI From 6 months up to approximately 36 months Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS
Changes in plasma Immunoglobulin level From Baseline until end of study up to 36 approximately months Changes in serum immunoglobulin level at the EOS compared to baseline
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 Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) From Baseline up to approximately 36 months Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS
Change in cognitive function From Baseline up to 36 approximately months Change in cognitive function from baseline to the EOS as assessed by the SDMT and CVLT-II where available
Change in plasma neurofilament light chain (NfL) From Baseline until end of study up to approximately 36 months - Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baselineC
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 Change in serum chitinase-3 like protein 1 (Chi3L1) - From Baseline until end of study up to approximately 36 months - Change in serum Chi3L1 levels at the EOS compared to baseline -
Trial Locations
- Locations (186)
CHI Saint Joseph Medical Group Neurology-Site Number:8400110
🇺🇸Lexington, Kentucky, United States
Investigational Site Number :3560005
🇮🇳Chandigarh, India
Investigational Site Number :6430007
🇷🇺Moscow, Russian Federation
Investigational Site Number :7240011
🇪🇸Sevilla, Andalucia, Spain
Investigational Site Number :7240010
🇪🇸Málaga, Spain
Meridian Clinical Research-Site Number:8400003
🇺🇸Savannah, Georgia, United States
Consultants In Neurology-Site Number:8400011
🇺🇸Northbrook, Illinois, United States
Fort Wayne Neurological Center-Site Number:8400039
🇺🇸Fort Wayne, Indiana, United States
Prairie Education and Research Cooperative-Site Number:8400071
🇺🇸Springfield, Illinois, United States
Jefferson Neurology Associates-Site Number:8400016
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number :7240009
🇪🇸Barakaldo, Bizkaia, Spain
Minneapolis Clinic of Neurology-Site Number:8400051
🇺🇸Minneapolis, Minnesota, United States
Sanford Brain & Spine Center-Site Number:8400126
🇺🇸Fargo, North Dakota, United States
Mountain Neurological Research Center, Inc.-Site Number:8400128
🇺🇸Basalt, Colorado, United States
Advanced Neurosciences Research-Site Number:8400025
🇺🇸Fort Collins, Colorado, United States
Investigational Site Number :8260016
🇬🇧Canterbury, Kent, United Kingdom
Investigational Site Number :0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
University of Miami-Site Number:8400063
🇺🇸Miami, Florida, United States
Investigational Site Number :0320005
🇦🇷San Miguel de Tucuman, Argentina
Investigational Site Number :0560004
🇧🇪Gent, Belgium
Investigational Site Number :1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520004
🇨🇱Valdivia, Chile
Investigational Site Number :2500005
🇫🇷Clermont Ferrand, France
Investigational Site Number :2500002
🇫🇷Nice, France
Investigational Site Number :2500003
🇫🇷Rennes, France
University of South Florida-Site Number:8400006
🇺🇸Tampa, Florida, United States
Investigational Site Number :1240002
🇨🇦Edmonton, Alberta, Canada
Investigational Site Number :0560001
🇧🇪Pelt, Belgium
Neurology Associates, PA-Site Number:8400004
🇺🇸Maitland, Florida, United States
International Neurorehabilitation Institute-Site Number:8400034
🇺🇸Lutherville-Timonium, Maryland, United States
Investigational Site Number :0320004
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number :0560005
🇧🇪Brugge, Belgium
Investigational Site Number :0760002
🇧🇷Curitiba, Brazil
Investigational Site Number :1240006
🇨🇦Gatineau, Canada
Investigational Site Number :1520006
🇨🇱Concepción, Chile
Investigational Site Number :2500018
🇫🇷Bordeaux, France
Investigational Site Number :2500006
🇫🇷Montpellier, France
Investigational Site Number :2500010
🇫🇷Nantes, France
Investigational Site Number :2500017
🇫🇷Nimes, France
South Florida Neurology Associates-Site Number:8400029
🇺🇸Boca Raton, Florida, United States
Investigational Site Number :0320001
🇦🇷Caba, Ciudad De Buenos Aires, Argentina
University Of Nebraska-Site Number:8400129
🇺🇸Omaha, Nebraska, United States
Investigational Site Number :0320002
🇦🇷Capital Federal, Buenos Aires, Argentina
University of Florida Health-Site Number:8400159
🇺🇸Gainesville, Florida, United States
Investigational Site Number :0560002
🇧🇪Mons, Belgium
Investigational Site Number :1240005
🇨🇦Greenfield Park, Quebec, Canada
Investigational Site Number :1520005
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Infinity Clinical Research-Site Number:8400008
🇺🇸Sunrise, Florida, United States
Investigational Site Number :3760001
🇮🇱Tel HaShomer, Israel
Investigational Site Number :3480105
🇭🇺Budapest, Hungary
Investigational Site Number :1240014
🇨🇦London, Ontario, Canada
Investigational Site Number :0320003
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 1240012
🇨🇦Hamilton, Ontario, Canada
Investigational Site Number :1240021
🇨🇦Quebec, Canada
Investigational Site Number :1520001
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1910001
🇭🇷Zagreb, Croatia
Investigational Site Number :1910002
🇭🇷Zagreb, Croatia
Investigational Site Number :2500019
🇫🇷Besancon, France
Investigational Site Number :2500004
🇫🇷Poissy, France
Investigational Site Number :3000004
🇬🇷Larissa, Greece
Investigational Site Number :3560008
🇮🇳Gurgaon, India
Investigational Site Number :3760003
🇮🇱Haifa, Israel
Investigational Site Number :3760004
🇮🇱Safed, Israel
Investigational Site Number :2500007
🇫🇷Paris, France
Investigational Site Number :2760014
🇩🇪Berlin, Germany
Investigational Site Number :1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :2760003
🇩🇪Würzburg, Germany
Investigational Site Number :3000009
🇬🇷Athens, Greece
Investigational Site Number :3560007
🇮🇳Gurgaon, India
Investigational Site Number :3760002
🇮🇱Ashkelon, Israel
Investigational Site Number :5780002
🇳🇴Namsos, Norway
Investigational Site Number :5780001
🇳🇴Oslo, Norway
San Juan MS Center-Site Number:8400015
🇵🇷Guaynabo, Puerto Rico
Investigational Site Number :6430011
🇷🇺Saransk, Russian Federation
Investigational Site Number :6430004
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number :6880006
🇷🇸Belgrade, Serbia
Investigational Site Number :6880002
🇷🇸Kragujevac, Serbia
Investigational Site Number :8040003
🇺🇦Vinnytsia, Ukraine
Investigational Site Number :7240013
🇪🇸Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number :2500001
🇫🇷Strasbourg, France
Investigational Site Number :3000001
🇬🇷Athens, Greece
Investigational Site Number :3000006
🇬🇷Athens, Greece
Investigational Site Number :3000003
🇬🇷Thessaloniki, Greece
Investigational Site Number :3480106
🇭🇺Kaposvár, Hungary
Investigational Site Number :3480103
🇭🇺Tatabánya, Hungary
Investigational Site Number :3760006
🇮🇱Rehovot, Israel
Investigational Site Number :4100003
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4280002
🇱🇻Riga, Latvia
Investigational Site Number :6200001
🇵🇹Braga, Portugal
Investigational Site Number :6200011
🇵🇹Lisboa, Portugal
Investigational Site Number :6880004
🇷🇸Nis, Serbia
Investigational Site Number :7030002
🇸🇰Martin, Slovakia
Investigational Site Number :7030004
🇸🇰Nitra, Slovakia
Investigational Site Number :7560003
🇨🇭Aarau, Switzerland
Investigational Site Number :7920006
🇹🇷Istanbul, Turkey
Investigational Site Number :7920004
🇹🇷Kuttahta, Turkey
Investigational Site Number :8040007
🇺🇦Kyiv, Ukraine
Investigational Site Number :8260003
🇬🇧Exeter, Devon, United Kingdom
Investigational Site Number :2760005
🇩🇪Bayreuth, Germany
Investigational Site Number :2760020
🇩🇪Bochum, Germany
Investigational Site Number :3560002
🇮🇳New Delhi, India
Investigational Site Number :4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :3000007
🇬🇷Athens, Greece
Investigational Site Number :4100001
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number :4280003
🇱🇻Riga, Latvia
Investigational Site Number :5280001
🇳🇱Amsterdam, Netherlands
Investigational Site Number :6880003
🇷🇸Belgrade, Serbia
Investigational Site Number :6880005
🇷🇸Novi Sad, Serbia
Investigational Site Number :7030001
🇸🇰Bratislava, Slovakia
Investigational Site Number :7920002
🇹🇷Ankara, Turkey
Investigational Site Number :7920003
🇹🇷Trabzon, Turkey
Investigational Site Number :3480102
🇭🇺Budapest, Hungary
Investigational Site Number :6200005
🇵🇹Coimbra, Portugal
Investigational Site Number :6200006
🇵🇹Lisboa, Portugal
Investigational Site Number :6430010
🇷🇺Kirov, Russian Federation
Investigational Site Number :6430003
🇷🇺Novosibirsk, Russian Federation
Investigational Site Number :6430002
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number :7560002
🇨🇭Bern, Switzerland
Investigational Site Number :8040020
🇺🇦Chernihiv, Ukraine
Investigational Site Number :8040002
🇺🇦Chernivtsi, Ukraine
Investigational Site Number :6200004
🇵🇹Santa Maria da Feira, Portugal
Investigational Site Number :6430012
🇷🇺Ekaterinburg, Russian Federation
Investigational Site Number :7560004
🇨🇭Lugano, Switzerland
Investigational Site Number :7920005
🇹🇷Besevler / Ankara, Turkey
Investigational Site Number :8040022
🇺🇦Kharkiv, Ukraine
Investigational Site Number :8040006
🇺🇦Lviv, Ukraine
Investigational Site Number :6430005
🇷🇺Moscow, Russian Federation
North Central Neurology Associates, PC-Site Number:8400009
🇺🇸Cullman, Alabama, United States
Arcadia Neurology Center-Site Number:8400070
🇺🇸Arcadia, California, United States
Center for Neurology and Spine-Site Number:8400089
🇺🇸Phoenix, Arizona, United States
Harbor UCLA-Site Number:8400088
🇺🇸Torrance, California, United States
Multiple Sclerosis Center of California-Site Number:8400135
🇺🇸Newport Beach, California, United States
Norton Neurology MS Services-Site Number:8400127
🇺🇸Louisville, Kentucky, United States
Saint Luke's Hospital-Site Number:8400153
🇺🇸Kansas City, Missouri, United States
University of Kentucky-Site Number:8400106
🇺🇸Lexington, Kentucky, United States
Wayne State University-Site Number:8400046
🇺🇸Detroit, Michigan, United States
The NeuroMedical Center-Site Number:8400057
🇺🇸Baton Rouge, Louisiana, United States
Meridian Clinical Research, LLC-Site Number:8400005
🇺🇸Raleigh, North Carolina, United States
University of New Mexico-Site Number:8400032
🇺🇸Albuquerque, New Mexico, United States
West Omaha Family Physicians-Site Number:8400139
🇺🇸Omaha, Nebraska, United States
Advanced Neuroscience Center-Site Number:8400035
🇺🇸Franklin, Tennessee, United States
Hackensack University Hospital-Site Number:8400047
🇺🇸Hackensack, New Jersey, United States
South Shore Neurologic Associates-Site Number:8400100
🇺🇸Patchogue, New York, United States
Novant Health Multiple Sclerosis Care Center - South Park-Site Number:8400120
🇺🇸Charlotte, North Carolina, United States
Neurological Associates-Site Number:8400097
🇺🇸Richmond, Virginia, United States
Dayton Center for Neurological Disorders-Site Number:8400081
🇺🇸Centerville, Ohio, United States
Mt Olympus Medical Research-Site Number:8400163
🇺🇸Katy, Texas, United States
Texas Institute for Neuroogical Disorders-Sherman-Site Number:8400151
🇺🇸Sherman, Texas, United States
Sibyl Wray, MD, Neurology, PC-Site Number:8400007
🇺🇸Knoxville, Tennessee, United States
Neurology Center of San Antonio-Site Number:8400036
🇺🇸San Antonio, Texas, United States
Premier Neurology-Site Number:8400069
🇺🇸Greer, South Carolina, United States
Wheaton Franciscan Healthcare-Site Number:8400022
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number :0760007
🇧🇷Sao Paulo, Brazil
Investigational Site Number :2030002
🇨🇿Brno, Czechia
Investigational Site Number :2030001
🇨🇿Jihlava, Czechia
Investigational Site Number :1910003
🇭🇷Zagreb, Croatia
Investigational Site Number :2030011
🇨🇿Hradec Kralove, Czechia
Investigational Site Number :2030005
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number :2500011
🇫🇷Bron, France
Investigational Site Number :2030008
🇨🇿Praha 10, Czechia
Investigational Site Number :2760015
🇩🇪Berlin, Germany
Investigational Site Number :2760012
🇩🇪Essen, Germany
Investigational Site Number :3000002
🇬🇷Athens, Greece
Investigational Site Number :3560004
🇮🇳Thiruvananthapuram, India
Investigational Site Number :4100006
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :6200002
🇵🇹Matosinhos, Portugal
Investigational Site Number :6200010
🇵🇹Porto, Portugal
Investigational Site Number :6430013
🇷🇺Bryansk, Russian Federation
Investigational Site Number :6430001
🇷🇺Kazan, Russian Federation
Investigational Site Number :6430006
🇷🇺Barnaul, Russian Federation
Investigational Site Number :6430014
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number :6880001
🇷🇸Belgrade, Serbia
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 :7240004
🇪🇸Salt, Girona [Gerona], Spain
Investigational Site Number :7240002
🇪🇸Madrid, Spain
Investigational Site Number :7240003
🇪🇸Madrid, Spain
Investigational Site Number :7240001
🇪🇸Madrid, Spain
Investigational Site Number :7240005
🇪🇸Lleida, Spain
Investigational Site Number :7240012
🇪🇸Pozuelo De Alarcón, Spain
Investigational Site Number :7920001
🇹🇷Samsun, Turkey
Investigational Site Number :8040019
🇺🇦Chernivtsi, Ukraine
Investigational Site Number :8040005
🇺🇦Dnipro, Ukraine
Investigational Site Number :8040018
🇺🇦Kharkiv, Ukraine
Investigational Site Number :8260009
🇬🇧Bristol, United Kingdom