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AzTrials

Relapsing Multiple SclerosisPhase 3GEMINI 1NCT04410978

Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)

A Phase 3 study testing Tolebrutinib and Teriflunomide in people with Relapsing Multiple Sclerosis, run by Sanofi at 179 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Relapsing Multiple Sclerosis
What is being tested?
Tolebrutinib and Teriflunomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
974 participants
Where
179 sitesin 24 countries
Study dates
30 Jun 2020to 15 Jul 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • ≥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)
  • 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

Who cannot join

  • The participant has been diagnosed with primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiple sclerosis (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, 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
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  • 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.

Trial locations and contacts

179 sites in 24 countries.

179 sites in 24 countries

China28 sites

  • Investigational Site Number :1560022

    Baotou, 014010

  • Investigational Site Number :1560006

    Beijing, 100034

  • Investigational Site Number :1560010

    Beijing, 100050

  • Investigational Site Number :1560012

    Beijing, 100053

  • Investigational Site Number :1560023

    Beijing, 100191

  • Investigational Site Number :1560001

    Beijing, 100730

  • Investigational Site Number :1560009

    Beijing, 100730

  • Investigational Site Number :1560025

    Beijing, 100730

  • Investigational Site Number :1560021

    Beijing, 100853

  • Investigational Site Number :1560004

    Changchun, 130021

  • Investigational Site Number :1560015

    Changsha, 410008

  • Investigational Site Number :1560005

    Chengdu, 610041

  • Investigational Site Number :1560019

    Chongqing, 400016

  • Investigational Site Number :1560035

    Fuzhou, 350005

  • Investigational Site Number :1560016

    Guangzhou, 510080

  • Investigational Site Number :1560028

    Guangzhou, 510515

  • Investigational Site Number :1560002

    Guangzhou, 510630

  • Investigational Site Number :1560027

    Hohhot, 010050

  • Investigational Site Number :1560044

    Nanjing, 210008

  • Investigational Site Number :1560042

    Nanjing, 210029

  • Investigational Site Number :1560003

    Shanghai, 200040

  • Investigational Site Number :1560018

    Shenyang, 110004

  • Investigational Site Number :1560014

    Shijiazhuang, 050000

  • Investigational Site Number :1560008

    Taiyuan, 030001

  • Investigational Site Number :1560020

    Tianjin, 300052

  • Investigational Site Number :1560011

    Wuhan, 430030

  • Investigational Site Number :1560017

    Xi'an, 710038

  • Investigational Site Number :1560033

    Yinchuan, 750004

Other trials in China

United States23 sites

  • University of Colorado-Site Number:8400012

    Aurora, Colorado, 80045

  • University of Alabama MS Center-Site Number:8400013

    Birmingham, Alabama, 35233

  • Tufts Medical Center-Site Number:8400072

    Boston, Massachusetts, 02111

  • The Ohio State University Wexner Medical Center-Site Number:8400150

    Columbus, Ohio, 43221

  • Optimed Research, LTD-Site Number:8400147

    Columbus, Ohio, 43235

  • University of Texas Southwestern Medical Center-Site Number:8400077

    Dallas, Texas, 75390

  • Michigan Institute For Neurological Disorders-Site Number:8400058

    Farmington Hills, Michigan, 48334

  • Beth Israel Deaconess Medical Center-Site Number:8400064

    Fort Myers, Florida, 33919

  • Consultants In Neurology-Site Number:8400011

    Northbrook, Illinois, 60062

  • Oklahoma Medical Research Foundation-Site Number:8400018

    Oklahoma City, Oklahoma, 73104

  • The Memorial Hospital-Site Number:8400033

    Owosso, Michigan, 48867

  • Sharlin Health & Neurology-Site Number:8400093

    Ozark, Missouri, 65721

  • Providence Multiple Sclerosis Center-Site Number:8400020

    Portland, Oregon, 97225

  • Meridian Clinical Research, LLC-Site Number:8400005

    Raleigh, North Carolina, 27607

  • University of San Francisco, Sandler Neurosciences Center-Site Number:8400137

    San Francisco, California, 94158

  • Meridian Clinical Research-Site Number:8400003

    Savannah, Georgia, 31406

  • Multiple Sclerosis Center, Swedish Neuroscience Institute-Site Number:8400121

    Seattle, Washington, 98122

  • Missouri Baptist Medical Center-Site Number:8400019

    St Louis, Missouri, 63131

  • Axiom Clinical Research of Florida-Site Number:8400001

    Tampa, Florida, 33609-4052

  • University of South Florida-Site Number:8400006

    Tampa, Florida, 33612

  • Georgetown University Medical Center-Site Number:8400119

    Washington D.C., District of Columbia, 20007

  • Columbus Neuroscience-Site Number:8400010

    Westerville, Ohio, 40382

  • Wake Forest University Baptist Medical Center-Site Number:8400116

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy14 sites

  • Investigational Site Number :3800011

    Bergamo, 24127

  • Investigational Site Number :3800015

    Catania, 95123

  • Investigational Site Number :3800012

    Florence, 50134

  • Investigational Site Number :3800014

    Genova, 16132

  • Investigational Site Number :3800001

    Milan, 20132

  • Investigational Site Number :3800010

    Milan, 20133

  • Investigational Site Number :3800003

    Naples, 80131

  • Investigational Site Number :3800006

    Naples, 80131

  • Investigational Site Number :3800007

    Orbassano, Torino, 10043

  • Investigational Site Number :3800008

    Pavia, 27100

  • Investigational Site Number :3800002

    Pozzilli, Isernia, 86077

  • Investigational Site Number :3800005

    Roma, 00152

  • Investigational Site Number :3800009

    Roma, 00168

  • Investigational Site Number :3800013

    Roma, 00189

Other trials in Italy

Japan14 sites

  • Investigational Site Number :3920014

    Bunkyo-ku, Tokyo, 113-8431

  • Investigational Site Number :3920016

    Chiba, Chiba, 260-8677

  • Investigational Site Number :3920018

    Kawagoe-shi, Saitama, 350-8550

  • Investigational Site Number :3920003

    Kodaira-shi, Tokyo, 187-8551

  • Investigational Site Number :3920008

    Koriyama-shi, Fukushima, 963-8052

  • Investigational Site Number :3920004

    Moriguchi-shi, Osaka, 570-8507

  • Investigational Site Number :3920022

    Morioka, Iwate, 020-8505

  • Investigational Site Number :3920005

    Niigata, Niigata, 951-8520

  • Investigational Site Number :3920001

    Osaka, Osaka, 556-0016

  • Investigational Site Number :3920010

    Ōta-ku, Tokyo, 146-0065

  • Investigational Site Number :3920023

    Sagamihara-shi, 252-0392

  • Investigational Site Number :3920013

    Shinjuku-ku, Tokyo, 162-8666

  • Investigational Site Number :3920012

    Tsukuba, Ibaraki, 305-0005

  • Investigational Site Number :3920009

    Ube-shi, Yamaguchi, 755-8505

Other trials in Japan

Russia12 sites

  • Investigational Site Number :6430014

    Krasnoyarsk, 660029

  • Investigational Site Number :6430002

    Moscow, 125367

  • Investigational Site Number :6430008

    Moscow, 129128

  • Investigational Site Number :6430011

    Nizhny Novgorod, 603137

  • Investigational Site Number :6430003

    Nizhny Novgorod, 603155

  • Investigational Site Number :6430007

    Pyatigorsk, 357538

  • Investigational Site Number :6430012

    Rostov-on-Don, 344022

  • Investigational Site Number :6430001

    Saint Petersburg, 194044

  • Investigational Site Number :6430005

    Samara, 443095

  • Investigational Site Number :6430009

    Smolensk, 214018

  • Investigational Site Number :6430006

    Tyumen, 625000

  • Investigational Site Number :6430004

    Ufa, 450005

Other trials in Russia

Turkey (Türkiye)10 sites

  • Investigational Site Number :7920005

    Eskişehir

  • Investigational Site Number :7920011

    Hatay

  • Investigational Site Number :7920002

    Istanbul, 34098

  • Investigational Site Number :7920009

    Istanbul, 34688

  • Investigational Site Number :7920007

    Istanbul, 34785

  • Investigational Site Number :7920003

    Istanbul

  • Investigational Site Number :7920008

    Izmir, 35100

  • Investigational Site Number :7920010

    Izmir

  • Investigational Site Number :7920001

    Kocaeli, 41380

  • Investigational Site Number :7920006

    Mersin, 33070

Other trials in Turkey (Türkiye)

Poland8 sites

  • Investigational Site Number :6160003

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Investigational Site Number :6160009

    Glogow Mlp., Podkarpackie Voivodeship, 36-060

  • Investigational Site Number :6160002

    Katowice, Silesian Voivodeship, 40-571

  • Investigational Site Number :6160004

    Katowice, Silesian Voivodeship, 40-686

  • Investigational Site Number :6160001

    Lodz, 90-549

  • Investigational Site Number :6160008

    Plewiska, Greater Poland Voivodeship, 62-064

  • Investigational Site Number :6160005

    Warsaw, Masovian Voivodeship, 01-211

  • Investigational Site Number :6160006

    Warsaw, Masovian Voivodeship, 01-684

Other trials in Poland

Romania8 sites

  • Investigational Site Number :6420015

    Brasov, 500283

  • Investigational Site Number :6420008

    Bucharest, 022328

  • Investigational Site Number :6420004

    Campulung Muscel, 115100

  • Investigational Site Number :6420003

    Constanța, 900123

  • Investigational Site Number :6420010

    Oradea, 410169

  • Investigational Site Number :6420005

    Sibiu, 550052

  • Investigational Site Number :6420001

    Târgu Mureş, 540136

  • Investigational Site Number :6420002

    Timișoara, 300736

Other trials in Romania

Spain8 sites

  • Investigational Site Number :7240009

    Barcelona, Barcelona [Barcelona], 08035

  • Investigational Site Number :7240004

    Córdoba, 14004

  • Investigational Site Number :7240008

    Donostia / San Sebastian, Basque Country, 20014

  • Investigational Site Number :7240005

    Málaga, 29010

  • Investigational Site Number :7240006

    Murcia, 30120

  • Investigational Site Number :7240001

    Pozuelo de Alarcón, Madrid, 28223

  • Investigational Site Number :7240003

    Seville, Andalusia, 41009

  • Investigational Site Number :7240007

    Valencia, 46026

Other trials in Spain

Ukraine8 sites

  • Investigational Site Number :8040011

    Ivano-Frankivsk, 76493

  • Investigational Site Number :8040016

    Kharkiv, 61068

  • Investigational Site Number :8040013

    Kharkiv, 61103

  • Investigational Site Number :8040008

    Kherson, 73000

  • Investigational Site Number :8040014

    Kyiv, 03115

  • Investigational Site Number :8040010

    Lutsk, 43005

  • Investigational Site Number :8040001

    Lviv, 79010

  • Investigational Site Number :8040009

    Odesa, 65025

Other trials in Ukraine

Bulgaria7 sites

  • Investigational Site Number :1000002

    Pleven, 5800

  • Investigational Site Number :1000005

    Plovdiv, 4000

  • Investigational Site Number :1000004

    Sofia, 1113

  • Investigational Site Number :1000008

    Sofia, 1407

  • Investigational Site Number :1000001

    Sofia, 1431

  • Investigational Site Number :1000006

    Sofia, 1431

  • Investigational Site Number :1000009

    Sofia, 1680

Other trials in Bulgaria

Germany6 sites

  • Investigational Site Number :2760001

    Dresden, 01307

  • Investigational Site Number :2760019

    Düsseldorf, 40225

  • Investigational Site Number :2760016

    Hamburg, 22179

  • Investigational Site Number :2760008

    Münster, 48149

  • Investigational Site Number :2760004

    Rostock, 18055

  • Investigational Site Number :2760011

    Ulm, 89081

Other trials in Germany

Taiwan5 sites

  • Investigational Site Number :1580007

    Hsinchu, 30059

  • Investigational Site Number :1580005

    Kaohsiung City, 833

  • Investigational Site Number :1580003

    Taichung, 402

  • Investigational Site Number :1580002

    Taipei, 112

  • Investigational Site Number :1580006

    Taoyuang, 333

Other trials in Taiwan

Canada4 sites

  • Investigational Site Number :1240006

    Gatineau, Quebec, J8Y 1W2

  • Investigational Site Number :1240003

    Ottawa, Ontario, K1H 8L6

  • Investigational Site Number :1240013

    Toronto, Ontario, M5B 1W8

  • Investigational Site Number :1240016

    Vancouver, British Columbia, V6T 2B5

Other trials in Canada

Czechia4 sites

  • Investigational Site Number :2030004

    Hradec Králové, 50005

  • Investigational Site Number :2030009

    Pardubice, 53203

  • Investigational Site Number :2030003

    Teplice, 415 29

  • Investigational Site Number :2030007

    Zlín, 76275

Other trials in Czechia

Lithuania4 sites

  • Investigational Site Number :4400003

    Kaunas, 50161

  • Investigational Site Number :4400002

    Klaipėda, 92288

  • Investigational Site Number :4400004

    Šiauliai, LT-76231

  • Investigational Site Number :4400001

    Vilnius, 08661

Other trials in Lithuania

Finland3 sites

  • Investigational Site Number :2460003

    Helsinki, 00180

  • Investigational Site Number :2460001

    Tampere, 33520

  • Investigational Site Number :2460002

    Turku, 20520

Other trials in Finland

Mexico3 sites

  • Investigational Site Number :4840002

    México, 03100

  • Investigational Site Number :4840001

    México, 06700

  • Investigational Site Number :4840003

    Veracruz, 91910

Other trials in Mexico

Belarus2 sites

  • Investigational Site Number :1120005

    Vitebsk, 210009

  • Investigational Site Number :1120004

    Vitebsk, 210037

Other trials in Belarus

Denmark2 sites

  • Investigational Site Number :2080001

    Esbjerg, 6700

  • Investigational Site Number :2080005

    Holstebro, 7500

Other trials in Denmark

Estonia2 sites

  • Investigational Site Number :2330001

    Tallinn, 11315

  • Investigational Site Number :2330002

    Tartu, 50406

Other trials in Estonia

Sweden2 sites

  • Investigational Site Number :7520001

    Gothenburg, 413 45

  • Investigational Site Number :7520002

    Stockholm, 113 65

Other trials in Sweden

Austria1 site

  • Investigational Site Number :0400004

    Linz, 4021

Other trials in Austria

Hong Kong1 site

  • Investigational Site Number : 3440001

    Shatin, NT

Other trials in Hong Kong

About this study

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

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

Read the detailed description

This was an event-driven (6-month confirmed disability worsening [CDW]) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 48 months).

Being tested
Tolebrutinib, Teriflunomide, Placebo to match Tolebrutinib, Placebo to match Teriflunomide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TolebrutinibDrug

    Also called SAR442168

    Pharmaceutical form: Tablet

    Route of administration: Oral

  • TeriflunomideDrug

    Pharmaceutical form: Tablet

    Route of administration: Oral

  • Placebo to match TolebrutinibDrug

    Pharmaceutical form: Tablet

    Route of administration: Oral

  • Placebo to match TeriflunomideDrug

    Pharmaceutical form: Tablet

    Route of administration: Oral

Study groups in NCT04410978
Study groupRoleWhat they receive
SAR442168Experimental60 mg oral SAR442168 + placebo to match the teriflunomide tablet once daily
Receives: Drug: Tolebrutinib; Drug: Placebo to match Teriflunomide
TeriflunomideActive comparator14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
Receives: Drug: Teriflunomide; Drug: Placebo to match Tolebrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses

    Multiple sclerosis (MS) relapse was defined as a monophasic, acute or subacute onset of new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for >=24 hours with or without recovery, present at normal body temperature, and preceded by >=30 days of clinical stability.

    Measured: Baseline (Day 1) to approximately 48 months

Secondary outcomes (16)

  1. Time to Onset of 6-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale

    The EDSS was a disability scale that assessed the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS score ranged from 0 (normal) to 10 (death due to MS), increasing in increments of 0.5 points. Higher scores indicated increased disability. Time to onset of 6-month CDW was defined as the time from randomization to the onset of a confirmed, sustained increase from baseline in EDSS score (of >=1.5 points when the baseline score was 0, of >=1.0 point when the baseline score was 0.5 to <=5.5, of >=0.5 points when the baseline EDSS score was >5.5) over at least 6 months that was not attributable to another etiology.

    Measured: Baseline (Day 1) to approximately 48 months

  2. Time to Onset of 3-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale

    The EDSS was a disability scale that assessed the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS score ranged from 0 (normal) to 10 (death due to MS), increasing in increments of 0.5 points. Higher scores indicated increased disability. Time to onset of 3-month CDW was defined as the time from randomization to the onset of a confirmed, sustained increase from baseline in EDSS score (of >=1.5 points when the baseline score was 0, of >=1.0 point when the baseline score was 0.5 to <=5.5, of >=0.5 points when the baseline EDSS score was >5.5) over at least 3 months that was not attributable to another etiology.

    Measured: Baseline (Day 1) to approximately 48 months

  3. Mean Number of New and/or Enlarging T2-Hyperintense Lesions Per Year

    Magnetic resonance imaging (MRI) of the brain was performed to identify number of new and/or enlarging T2-hyperintense lesions defined as the sum of the individual number of new and/or enlarging T2 lesions starting from baseline up to and including the EOS visit.

    Measured: Baseline (Day 1) to approximately 48 months

  4. Mean Number of New Gadolinium-Enhancing T1-Hyperintense Lesions Per Scan

    MRI of the brain was performed to identify number of new Gd-enhancing T1-hyperintense lesions defined as the sum of the individual number of new Gd- enhancing T1-hyperintense lesions starting from baseline up to and including the EOS visit.

    Measured: Baseline (Day 1) to approximately 48 months

  5. Change From Baseline in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT) at EOS

    The SDMT was used to assess processing speed, divided attention, visual scanning, tracking and motor speed. It involved a simple substitution task using a reference key. The number of correct substitutions and number of items completed within a 90 second interval (maximum 110 seconds) were recorded. A decrease of 4 points from baseline on the SDMT was considered meaningful worsening. The score was the number of correctly coded items from 0-110 in 90 seconds; higher scores indicating a better outcome. Baseline was defined as the last available value prior to the first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

  6. Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test Second Edition (CVLT-II) at EOS

    The CVLT-II was a verbal learning and memory test consisting of recall and recognition of a list of 16 words. For each assessment, 5 trials were completed. Total Correct Recall Trials 1-5 was scaled to a normalized T-score metric, which had a mean of 50 and standard deviation of 10, the maximum possible score was 80 and a minimum was 0. Higher values indicated improved cognitive function. Baseline was defined as the last available value prior to the first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

  7. Time to Onset of 6-Month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale

    The EDSS was a disability scale that assessed the following 7 functional domains: visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder. The total EDSS score ranged from 0 (normal) to 10 (death due to MS), increasing in increments of 0.5 points. Higher scores indicated increased disability. CDI was defined as a decrease of >=1 point from baseline in the EDSS score lasting at least 6 months.

    Measured: Baseline (Day 1) to approximately 48 months

  8. Percent Change in Brain Volume Loss at EOS Compared to Month 6

    MRI of the brain was performed at the specified timepoints to detect the changes in brain volume loss.

    Measured: Month 6 to EOS (up to approximately 48 months)

  9. Change From Baseline in Multiple Sclerosis Quality of Life 54 (MSQoL-54) Questionnaire Score at EOS

    MSQoL-54 was standardized instrument comprising generic and MS-specific items. This 54-item instrument generated 12 subscales and 2 single-item measures (satisfaction with sexual function [1 item]; change in health [1 item]). 12 subscales were: a: physical health (10 items), b: health perceptions (5 items), c: energy (5 items), d: role limit physical (4 items), e: sexual function (4 items), f: pain (3 items), g: social function (3 items), h: health distress (4 items), i: overall quality of life (2 items), j: emotional well-being (5 items), k: role limitations emotional (3 items) and l: cognitive function (4 items). Physical and mental health composite score were calculated as weighted sum of 'a to h' and 'i to l' subscales respectively. Each composite score was transformed linearly to common 0 (worst) to 100 (best) score range; higher score indicated improved quality of life. Baseline was defined as last available value prior to first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

  10. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), TEAEs Leading to Permanent Study Intervention Discontinuation and Treatment-emergent Adverse Events of Special Interest (AESIs)

    An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.

    Measured: From first dose of study intervention (Day 1) up to the earliest of either 10 days post last dose, death or last contact; up to approximately 48 months

  11. Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess Cmax of tolebrutinib and M2 metabolite using population pharmacokinetic (PK) model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  12. Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess Tmax of tolebrutinib and M2 metabolite using population PK model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  13. Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite

    Blood samples were collected at specified timepoints to assess AUC0-24 of tolebrutinib and M2 metabolite using population PK model.

    Measured: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12

  14. Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS

    Blood samples were collected at specified timepoints to assess change from baseline in NfL and Chi3L1. Baseline was defined as the last available value prior to the first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

  15. Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS

    Blood samples were collected at specified timepoints to assess change from baseline in CD19+ B cells. Baseline was defined as the last available value prior to the first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

  16. Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS

    Blood samples were collected at specified timepoints to assess change from baseline in IgG and IgM levels. Baseline was defined as the last available value prior to the first dose of study intervention.

    Measured: Baseline (Day 1) to EOS (up to approximately 48 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2020
  2. Study start30 Jun 2020
  3. Primary completion15 Jul 2024
  4. Study completion15 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
974 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04410978
Sponsor's protocol ID
EFC16033
Other IDs
U1111-1238-1418, 2020-000637-41
Acronym
GEMINI 1
Status last verified
Jun 2025
First submitted
28 May 2020
Last updated
2 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Publications

  • Maxwell CR, Turner TJ, Wallstroem E, Patel S, Pappas SC, Lewis JH, Andrade RJ, Syed S. Tolebrutinib liver safety: A detailed overview. Mult Scler Relat Disord. 2026 Jul 23;113:107404. doi: 10.1016/j.msard.2026.107404. Online ahead of print.

    PubMed 42546561

  • Oh J, Arnold DL, Cree BAC, Ionete C, Kim HJ, Sormani MP, Syed S, Chen Y, Maxwell CR, Benoit P, Turner TJ, Wallstroem E, Wiendl H; Tolebrutinib Phase 3 GEMINI 1 and 2 Trial Group. Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2025 May 15;392(19):1893-1904. doi: 10.1056/NEJMoa2415985. Epub 2025 Apr 8.

    PubMed 40202623

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tolebrutinib and Teriflunomide in people with Relapsing Multiple Sclerosis, run by Sanofi at 179 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 179 sites in China, United States, Italy, Japan, Russia and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses (time frame: Baseline (Day 1) to approximately 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04410978, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.

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