Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Drug: Placebo to match Tolebrutinib
- Registration Number
- NCT04410978
- 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 population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety 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 + 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 + placebo to match the teriflunomide tablet once daily
- Primary Outcome Measures
Name Time Method Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses Up to approximately 36 months Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses
- Secondary Outcome Measures
Name Time Method Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months Up to approximately 36 months Time to onset of confirmed disability worsening confirmed over at least 6 months Up to approximately 36 months Time 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.Change in cognitive function From Baseline up to approximately 36 months Change in cognitive function from baseline to the end of study (EOS) as assessed by SDMT and by CVLT-II where available
Population Pharmacokinetics Concentration of SAR442168 and relevant metabolites at 9 Months 9 Months Plasma concentration of SAR442168 (population PK assessment) at 9 Months
Population Pharmacokinetics - Concentration of SAR442168 and relevant metabolites at 12 Months 12 Months Plasma concentration of SAR442168 (population PK assessment) at 12 Months
Population Pharmacokinetics - Concentration SAR442168 and relevant metabolites at 6 months 6 Months Plasma concentration of SAR442168 (population PK assessment) at 6 Months
Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study (EOS) From 6 months up to approximately 36 months Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS From 6 months up to approximately 36 months 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
Percent Change in Brain volume loss (BVL) From 6 months up to approximately 36 months Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS
Change in plasma NfL From Baseline until end of study approximately 36 months Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baseline
Change in lymphocyte Phenotype From Baseline until end of study approximately 36 months Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants
Change in Multiple Sclerosis Quality of Life From Baseline up to approximately 36 months Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS
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 CHI3L1 levels From Baseline until end of study approximately 36 months Change in serum Chi3L1 levels at the EOS compared to baseline
Changes in plasma Immunoglobulin levels From Baseline until end of study (up to 36 months) Changes in serum immunoglobulin level at the EOS compared to baseline
Trial Locations
- Locations (179)
University of Texas Southwestern Medical Center-Site Number:8400077
🇺🇸Dallas, Texas, United States
Meridian Clinical Research-Site Number:8400003
🇺🇸Savannah, Georgia, United States
Investigational Site Number :1000001
🇧🇬Sofia, Bulgaria
Investigational Site Number :2030009
🇨🇿Pardubice, Czechia
Investigational Site Number :2030007
🇨🇿Zlin, Czechia
Investigational Site Number :6430009
🇷🇺Smolensk, Russian Federation
Investigational Site Number :7920002
🇹🇷Istanbul, Turkey
Optimed Research, LTD-Site Number:8400147
🇺🇸Columbus, Ohio, United States
Multiple Sclerosis Center, Swedish Neuroscience Institute-Site Number:8400121
🇺🇸Seattle, Washington, United States
Investigational Site Number :1560010
🇨🇳Beijing, China
Investigational Site Number :1560001
🇨🇳Beijing, China
Investigational Site Number :2080005
🇩🇰Holstebro, Denmark
Investigational Site Number :1120004
🇧🇾Vitebsk, Belarus
Investigational Site Number :6420004
🇷🇴Campulung, Romania
Investigational Site Number :6420003
🇷🇴Constanta, Romania
Investigational Site Number :8040011
🇺🇦Ivano-Frankivsk, Ukraine
Investigational Site Number :1000008
🇧🇬Sofia, Bulgaria
Investigational Site Number :3920012
🇯🇵Tsukuba-shi, Ibaraki, Japan
Investigational Site Number :3920001
🇯🇵Osaka-shi, Osaka, Japan
Investigational Site Number :6160009
🇵🇱Glogow Mlp., Podkarpackie, Poland
Investigational Site Number :6160002
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number :1240006
🇨🇦Gatineau, Quebec, Canada
Investigational Site Number :1000005
🇧🇬Plovdiv, Bulgaria
Investigational Site Number :2460002
🇫🇮Turku, Finland
Investigational Site Number :3920008
🇯🇵Koriyama-shi, Fukushima, Japan
Investigational Site Number :3920010
🇯🇵Ota-ku, Tokyo, Japan
Investigational Site Number :3920023
🇯🇵Sagamihara-shi, Japan
Investigational Site Number :0400004
🇦🇹Linz, Austria
Investigational Site Number :1000004
🇧🇬Sofia, Bulgaria
Investigational Site Number :2460001
🇫🇮Tampere, Finland
Georgetown University Medical Center-Site Number:8400119
🇺🇸Washington, District of Columbia, United States
Investigational Site Number :1000002
🇧🇬Pleven, Bulgaria
Investigational Site Number :6160004
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number :1240016
🇨🇦Vancouver, British Columbia, Canada
Investigational Site Number :3920022
🇯🇵Morioka-shi, Iwate, Japan
Investigational Site Number :3920004
🇯🇵Moriguchi-shi, Osaka, Japan
Investigational Site Number :4400004
🇱🇹Siauliai, Lithuania
Investigational Site Number :6420008
🇷🇴Bucuresti, Romania
Investigational Site Number :6420010
🇷🇴Oradea, Romania
Investigational Site Number :6160005
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number :6420005
🇷🇴Sibiu, Romania
Investigational Site Number :6430006
🇷🇺Tyumen, Russian Federation
Investigational Site Number :6430012
🇷🇺Rostov-on-Don, Russian Federation
Investigational Site Number :8040010
🇺🇦Lutsk, Ukraine
Investigational Site Number :1580005
🇨🇳Kaohsiung, Taiwan
Investigational Site Number :8040014
🇺🇦Kyiv, Ukraine
Investigational Site Number :8040001
🇺🇦Lviv, Ukraine
Investigational Site Number :8040016
🇺🇦Kharkiv, Ukraine
Investigational Site Number :8040013
🇺🇦Kharkiv, Ukraine
Investigational Site Number :8040008
🇺🇦Kherson, Ukraine
Investigational Site Number :1580006
🇨🇳Taoyuang, Taiwan
Investigational Site Number :8040009
🇺🇦Odesa, Ukraine
Investigational Site Number :3800010
🇮🇹Milano, Italy
Investigational Site Number :3800009
🇮🇹Roma, Italy
Investigational Site Number :3800003
🇮🇹Napoli, Italy
Investigational Site Number :3800008
🇮🇹Pavia, Italy
Investigational Site Number :3800013
🇮🇹Roma, Italy
Investigational Site Number :1240003
🇨🇦Ottawa, Ontario, Canada
Axiom Clinical Research of Florida-Site Number:8400001
🇺🇸Tampa, Florida, United States
Providence Multiple Sclerosis Center-Site Number:8400020
🇺🇸Portland, Oregon, United States
University of Alabama MS Center-Site Number:8400013
🇺🇸Birmingham, Alabama, United States
University of San Francisco, Sandler Neurosciences Center-Site Number:8400137
🇺🇸San Francisco, California, United States
University of Colorado-Site Number:8400012
🇺🇸Aurora, Colorado, United States
University of South Florida-Site Number:8400006
🇺🇸Tampa, Florida, United States
Oklahoma Medical Research Foundation-Site Number:8400018
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number :1560021
🇨🇳Beijing, China
Beth Israel Deaconess Medical Center-Site Number:8400064
🇺🇸Fort Myers, Florida, United States
Consultants In Neurology-Site Number:8400011
🇺🇸Northbrook, Illinois, United States
Tufts Medical Center-Site Number:8400072
🇺🇸Boston, Massachusetts, United States
The Memorial Hospital-Site Number:8400033
🇺🇸Owosso, Michigan, United States
Michigan Institute For Neurological Disorders-Site Number:8400058
🇺🇸Farmington Hills, Michigan, United States
Sharlin Health & Neurology-Site Number:8400093
🇺🇸Ozark, Missouri, United States
Missouri Baptist Medical Center-Site Number:8400019
🇺🇸Saint Louis, Missouri, United States
Meridian Clinical Research, LLC-Site Number:8400005
🇺🇸Raleigh, North Carolina, United States
The Ohio State University Wexner Medical Center-Site Number:8400150
🇺🇸Columbus, Ohio, United States
Wake Forest University Baptist Medical Center-Site Number:8400116
🇺🇸Winston-Salem, North Carolina, United States
Columbus Neuroscience-Site Number:8400010
🇺🇸Westerville, Ohio, United States
Investigational Site Number :1120005
🇧🇾Vitebsk, Belarus
Investigational Site Number :1000009
🇧🇬Sofia, Bulgaria
Investigational Site Number :1560006
🇨🇳Beijing, China
Investigational Site Number :1000006
🇧🇬Sofia, Bulgaria
Investigational Site Number :1240013
🇨🇦Toronto, Ontario, Canada
Investigational Site Number :1560022
🇨🇳Baotou, China
Investigational Site Number :1560003
🇨🇳Shanghai, China
Investigational Site Number :1560012
🇨🇳Beijing, China
Investigational Site Number :1560023
🇨🇳Beijing, China
Investigational Site Number :1560009
🇨🇳Beijing, China
Investigational Site Number :1560004
🇨🇳Changchun, China
Investigational Site Number :1560025
🇨🇳Beijing, 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 :1560016
🇨🇳Guangzhou, China
Investigational Site Number :1560002
🇨🇳Guangzhou, China
Investigational Site Number :1560027
🇨🇳Hohhot, China
Investigational Site Number :1560028
🇨🇳Guangzhou, China
Investigational Site Number :1560044
🇨🇳Nanjing, China
Investigational Site Number :1560014
🇨🇳Shijiazhuang, China
Investigational Site Number :1560042
🇨🇳Nanjing, China
Investigational Site Number :1560018
🇨🇳Shenyang, China
Investigational Site Number :1560008
🇨🇳Taiyuan, China
Investigational Site Number :1560020
🇨🇳Tianjin, China
Investigational Site Number :1560011
🇨🇳Wuhan, China
Investigational Site Number :1560017
🇨🇳Xi'an, China
Investigational Site Number :2030004
🇨🇿Hradec Kralove, Czechia
Investigational Site Number :1560033
🇨🇳Yinchuan, China
Investigational Site Number :2030003
🇨🇿Teplice, Czechia
Investigational Site Number :2080001
🇩🇰Esbjerg, Denmark
Investigational Site Number :2330001
🇪🇪Tallinn, Estonia
Investigational Site Number :2330002
🇪🇪Tartu, Estonia
Investigational Site Number :2460003
🇫🇮Helsinki, Finland
Investigational Site Number :2760019
🇩🇪Düsseldorf, Germany
Investigational Site Number :2760001
🇩🇪Dresden, Germany
Investigational Site Number :2760004
🇩🇪Rostock, Germany
Investigational Site Number :2760016
🇩🇪Hamburg, Germany
Investigational Site Number :2760008
🇩🇪Münster, Germany
Investigational Site Number :3800007
🇮🇹Orbassano, Torino, Italy
Investigational Site Number :3800012
🇮🇹Firenze, Italy
Investigational Site Number :3800002
🇮🇹Pozzilli, Isernia, Italy
Investigational Site Number :2760011
🇩🇪Ulm, Germany
Investigational Site Number :3800015
🇮🇹Catania, Italy
Investigational Site Number :3800011
🇮🇹Bergamo, Italy
Investigational Site Number :3800014
🇮🇹Genova, Italy
Investigational Site Number :3800001
🇮🇹Milano, Italy
Investigational Site Number :3800006
🇮🇹Napoli, Italy
Investigational Site Number :3800005
🇮🇹Roma, Italy
Investigational Site Number :3920016
🇯🇵Chiba-shi, Chiba, Japan
Investigational Site Number :3920005
🇯🇵Niigata-shi, Niigata, Japan
Investigational Site Number :3920014
🇯🇵Bunkyo-ku, Tokyo, Japan
Investigational Site Number :3920013
🇯🇵Shinjuku-ku, Tokyo, Japan
Investigational Site Number :3920003
🇯🇵Kodaira-shi, Tokyo, Japan
Investigational Site Number :3920018
🇯🇵Kawagoe-shi, Saitama, Japan
Investigational Site Number :3920009
🇯🇵Ube-shi, Yamaguchi, Japan
Investigational Site Number :4400003
🇱🇹Kaunas, Lithuania
Investigational Site Number :4400002
🇱🇹Klaipeda, Lithuania
Investigational Site Number :4400001
🇱🇹Vilnius, Lithuania
Investigational Site Number :4840002
🇲🇽Mexico, Mexico
Investigational Site Number :4840001
🇲🇽Mexico, Mexico
Investigational Site Number :4840003
🇲🇽Veracruz, Mexico
Investigational Site Number :6160003
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Investigational Site Number :6160006
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number :6160008
🇵🇱Plewiska, Wielkopolskie, Poland
Investigational Site Number :6160001
🇵🇱Lodz, Poland
Investigational Site Number :6420015
🇷🇴Brasov, Romania
Investigational Site Number :6420001
🇷🇴Targu Mures, Romania
Investigational Site Number :6420002
🇷🇴Timisoara, Romania
Investigational Site Number :6430014
🇷🇺Krasnoyarsk, Russian Federation
Investigational Site Number :6430002
🇷🇺Moscow, Russian Federation
Investigational Site Number :6430008
🇷🇺Moscow, Russian Federation
Investigational Site Number :6430011
🇷🇺Nizhny Novgorod, Russian Federation
Investigational Site Number :6430003
🇷🇺Nizhny Novgorod, Russian Federation
Investigational Site Number :6430005
🇷🇺Samara, Russian Federation
Investigational Site Number :6430007
🇷🇺Pyatigorsk, Russian Federation
Investigational Site Number :6430001
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number :6430004
🇷🇺Ufa, Russian Federation
Investigational Site Number :7240003
🇪🇸Sevilla, Andalucia, Spain
Investigational Site Number :7240001
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Investigational Site Number :7240009
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240008
🇪🇸Donostia, Pais Vasco, Spain
Investigational Site Number :7240004
🇪🇸Córdoba, Spain
Investigational Site Number :7240006
🇪🇸Murcia, Spain
Investigational Site Number :7520002
🇸🇪Stockholm, Sweden
Investigational Site Number :7240005
🇪🇸Málaga, Spain
Investigational Site Number :7520001
🇸🇪Göteborg, Sweden
Investigational Site Number :1580003
🇨🇳Taichung, Taiwan
Investigational Site Number :1580007
🇨🇳Hsinchu City, Taiwan
Investigational Site Number :7240007
🇪🇸Valencia, Spain
Investigational Site Number :1580002
🇨🇳Taipei, Taiwan
Investigational Site Number :7920005
🇹🇷Eskisehir, Turkey
Investigational Site Number :7920008
🇹🇷Izmir, Turkey
Investigational Site Number :7920010
🇹🇷Izmir, Turkey
Investigational Site Number :7920011
🇹🇷Hatay, Turkey
Investigational Site Number :7920009
🇹🇷Istanbul, Turkey
Investigational Site Number :7920007
🇹🇷Istanbul, Turkey
Investigational Site Number :7920003
🇹🇷Istanbul, Turkey
Investigational Site Number :7920001
🇹🇷Kocaeli, Turkey
Investigational Site Number :7920006
🇹🇷Mersin, Turkey
Investigational Site Number : 3440001
🇭🇰Shatin, NT, Hong Kong