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Relapsing Multiple SclerosisPhase 3GEMINI 2NCT04410991

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

A Phase 3 study testing Tolebrutinib and Teriflunomide HMR1726 in people with Relapsing Multiple Sclerosis, run by Sanofi at 186 sites in 28 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 HMR1726
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
899 participants
Where
186 sitesin 28 countries
Study dates
11 Jun 2020to 16 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
Show all 21Show fewer
  • ≥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

Who cannot join

  • 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
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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

186 sites in 28 countries.

186 sites in 28 countries

United States43 sites

  • University of New Mexico-Site Number:8400032

    Albuquerque, New Mexico, 87131

  • Arcadia Neurology Center-Site Number:8400070

    Arcadia, California, 91006

  • Mountain Neurological Research Center, Inc.-Site Number:8400128

    Basalt, Colorado, 81621

  • The NeuroMedical Center-Site Number:8400057

    Baton Rouge, Louisiana, 70810

  • South Florida Neurology Associates-Site Number:8400029

    Boca Raton, Florida, 33487

  • Dayton Center for Neurological Disorders-Site Number:8400081

    Centerville, Ohio, 45459

  • Novant Health Multiple Sclerosis Care Center - South Park-Site Number:8400120

    Charlotte, North Carolina, 28210

  • North Central Neurology Associates, PC-Site Number:8400009

    Cullman, Alabama, 35058

  • Wayne State University-Site Number:8400046

    Detroit, Michigan, 48201

  • Sanford Brain & Spine Center-Site Number:8400126

    Fargo, North Dakota, 58103

  • Advanced Neurosciences Research-Site Number:8400025

    Fort Collins, Colorado, 80528

  • Fort Wayne Neurological Center-Site Number:8400039

    Fort Wayne, Indiana, 46804

  • Advanced Neuroscience Center-Site Number:8400035

    Franklin, Tennessee, 37064

  • University of Florida Health-Site Number:8400159

    Gainesville, Florida, 32608

  • Premier Neurology-Site Number:8400069

    Greer, South Carolina, 29650

  • Hackensack University Hospital-Site Number:8400047

    Hackensack, New Jersey, 07601

  • Saint Luke's Hospital-Site Number:8400153

    Kansas City, Missouri, 64111

  • Mt Olympus Medical Research-Site Number:8400163

    Katy, Texas, 77450

  • Sibyl Wray, MD, Neurology, PC-Site Number:8400007

    Knoxville, Tennessee, 37922

  • CHI Saint Joseph Medical Group Neurology-Site Number:8400110

    Lexington, Kentucky, 40509

  • University of Kentucky-Site Number:8400106

    Lexington, Kentucky, 40536

  • Norton Neurology MS Services-Site Number:8400127

    Louisville, Kentucky, 40207

  • International Neurorehabilitation Institute-Site Number:8400034

    Lutherville-Timonium, Maryland, 21093

  • Neurology Associates, PA-Site Number:8400004

    Maitland, Florida, 32761

  • University of Miami-Site Number:8400063

    Miami, Florida, 33136

  • Wheaton Franciscan Healthcare-Site Number:8400022

    Milwaukee, Wisconsin, 53215

  • Minneapolis Clinic of Neurology-Site Number:8400051

    Minneapolis, Minnesota, 55422

  • Multiple Sclerosis Center of California-Site Number:8400135

    Newport Beach, California, 92663

  • Consultants In Neurology-Site Number:8400011

    Northbrook, Illinois, 60062

  • West Omaha Family Physicians-Site Number:8400139

    Omaha, Nebraska, 68130

  • University Of Nebraska-Site Number:8400129

    Omaha, Nebraska, 68198

  • South Shore Neurologic Associates-Site Number:8400100

    Patchogue, New York, 11772

  • Jefferson Neurology Associates-Site Number:8400016

    Philadelphia, Pennsylvania, 19107

  • Center for Neurology and Spine-Site Number:8400089

    Phoenix, Arizona, 84018

  • Meridian Clinical Research, LLC-Site Number:8400005

    Raleigh, North Carolina, 27607

  • Neurological Associates-Site Number:8400097

    Richmond, Virginia, 23229

  • Neurology Center of San Antonio-Site Number:8400036

    San Antonio, Texas, 78258

  • Meridian Clinical Research-Site Number:8400003

    Savannah, Georgia, 31406

  • Texas Institute for Neuroogical Disorders-Sherman-Site Number:8400151

    Sherman, Texas, 75092

  • Prairie Education and Research Cooperative-Site Number:8400071

    Springfield, Illinois, 62701

  • Infinity Clinical Research-Site Number:8400008

    Sunrise, Florida, 33351

  • University of South Florida-Site Number:8400006

    Tampa, Florida, 33612

  • Harbor UCLA-Site Number:8400088

    Torrance, California, 90502

Other trials in United States

Spain13 sites

  • Investigational Site Number :7240008

    A Coruña, 15006

  • Investigational Site Number :7240009

    Barakaldo, Bizkaia, 48903

  • Investigational Site Number :7240006

    Barcelona, Barcelona [Barcelona], 08036

  • Investigational Site Number :7240007

    L'Hospitalet de Llobregat, 08907

  • Investigational Site Number :7240013

    Las Palmas de Gran Canaria, Las Palmas, 35010

  • Investigational Site Number :7240005

    Lleida, 25198

  • Investigational Site Number :7240003

    Madrid, 28007

  • Investigational Site Number :7240001

    Madrid, 28034

  • Investigational Site Number :7240002

    Madrid, 28040

  • Investigational Site Number :7240010

    Málaga, 29010

  • Investigational Site Number :7240012

    Pozuelo de Alarcón, 28223

  • Investigational Site Number :7240004

    Salt, Girona [Gerona], 17190

  • Investigational Site Number :7240011

    Seville, Andalusia, 41009

Other trials in Spain

France12 sites

  • Investigational Site Number :2500019

    Besançon, 25000

  • Investigational Site Number :2500018

    Bordeaux

  • Investigational Site Number :2500011

    Bron, 69500

  • Investigational Site Number :2500005

    Clermont-Ferrand, 63003

  • Investigational Site Number :2500006

    Montpellier, 34295

  • Investigational Site Number :2500010

    Nantes, 44093

  • Investigational Site Number :2500002

    Nice, 06002

  • Investigational Site Number :2500017

    Nîmes, 30029

  • Investigational Site Number :2500007

    Paris, 75019

  • Investigational Site Number :2500004

    Poissy, 78300

  • Investigational Site Number :2500003

    Rennes, 35033

  • Investigational Site Number :2500001

    Strasbourg, 67098

Other trials in France

Russia12 sites

  • Investigational Site Number :6430006

    Barnaul, 656024

  • Investigational Site Number :6430013

    Bryansk, 241033

  • Investigational Site Number :6430001

    Kazan', 420021

  • Investigational Site Number :6430010

    Kirov, 610998

  • Investigational Site Number :6430007

    Moscow, 117997

  • Investigational Site Number :6430005

    Moscow, 127015

  • Investigational Site Number :6430003

    Novosibirsk, 630087

  • Investigational Site Number :6430014

    Saint Petersburg, 192242

  • Investigational Site Number :6430004

    Saint Petersburg, 197022

  • Investigational Site Number :6430002

    Saint Petersburg, 197110

  • Investigational Site Number :6430011

    Saransk, 430032

  • Investigational Site Number :6430012

    Yekaterinburg, 620102

Other trials in Russia

Ukraine9 sites

  • Investigational Site Number :8040020

    Chernihiv, 14029

  • Investigational Site Number :8040002

    Chernivtsi, 58000

  • Investigational Site Number :8040019

    Chernivtsi, 58023

  • Investigational Site Number :8040005

    Dnipro, 49005

  • Investigational Site Number :8040022

    Kharkiv, 61103

  • Investigational Site Number :8040018

    Kharkiv, 61166

  • Investigational Site Number :8040007

    Kyiv, 02091

  • Investigational Site Number :8040006

    Lviv, 79013

  • Investigational Site Number :8040003

    Vinnytsia, 21050

Other trials in Ukraine

Greece7 sites

  • Investigational Site Number :3000001

    Athens, 115 28

  • Investigational Site Number :3000006

    Athens, 11535

  • Investigational Site Number :3000002

    Athens, 12462

  • Investigational Site Number :3000007

    Athens, 15125

  • Investigational Site Number :3000009

    Athens

  • Investigational Site Number :3000004

    Larissa, 41110

  • Investigational Site Number :3000003

    Thessaloniki, 546 36

Other trials in Greece

Portugal7 sites

  • Investigational Site Number :6200001

    Braga, 4710-243

  • Investigational Site Number :6200005

    Coimbra, 3000-075

  • Investigational Site Number :6200011

    Lisbon, 1162-050

  • Investigational Site Number :6200006

    Lisbon, 1649-035

  • Investigational Site Number :6200002

    Matosinhos Municipality, 4464-513

  • Investigational Site Number :6200010

    Porto, 4099-001

  • Investigational Site Number :6200004

    Santa Maria da Feira, 4520-211

Other trials in Portugal

Canada6 sites

  • Investigational Site Number :1240002

    Edmonton, Alberta, T6G 2C8

  • Investigational Site Number :1240006

    Gatineau, J8Y1W2

  • Investigational Site Number :1240005

    Greenfield Park, Quebec, J4V 2J2

  • Investigational Site Number : 1240012

    Hamilton, Ontario, L8L 2X2

  • Investigational Site Number :1240014

    London, Ontario, N6A 5A5

  • Investigational Site Number :1240021

    Québec, G1W 4R4

Other trials in Canada

Chile6 sites

  • Investigational Site Number :1520006

    Concepción

  • Investigational Site Number :1520002

    Santiago, Reg Metropolitana de Santiago, 7650568

  • Investigational Site Number :1520005

    Santiago, Reg Metropolitana de Santiago, 833-0024

  • Investigational Site Number :1520001

    Santiago, Reg Metropolitana de Santiago, 8380456

  • Investigational Site Number :1520003

    Santiago, Reg Metropolitana de Santiago, 8431657

  • Investigational Site Number :1520004

    Valdivia, 5110683

Other trials in Chile

Germany6 sites

  • Investigational Site Number :2760005

    Bayreuth, 95445

  • Investigational Site Number :2760015

    Berlin, 10713

  • Investigational Site Number :2760014

    Berlin, 12099

  • Investigational Site Number :2760020

    Bochum, 44791

  • Investigational Site Number :2760012

    Essen, 45147

  • Investigational Site Number :2760003

    Würzburg, 97070

Other trials in Germany

Serbia6 sites

  • Investigational Site Number :6880001

    Belgrade, 11000

  • Investigational Site Number :6880003

    Belgrade, 11000

  • Investigational Site Number :6880006

    Belgrade, 11000

  • Investigational Site Number :6880002

    Kragujevac, 34000

  • Investigational Site Number :6880004

    Niš, 18000

  • Investigational Site Number :6880005

    Novi Sad, 21000

Other trials in Serbia

Turkey (Türkiye)6 sites

  • Investigational Site Number :7920002

    Ankara, 06100

  • Investigational Site Number :7920005

    Besevler / Ankara, 06500

  • Investigational Site Number :7920006

    Istanbul, 34896

  • Investigational Site Number :7920004

    Kuttahta, 43100

  • Investigational Site Number :7920001

    Samsun

  • Investigational Site Number :7920003

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Argentina5 sites

  • Investigational Site Number :0320004

    CABA, Buenos Aires, C1023AAB

  • Investigational Site Number :0320001

    CABA, Buenos Aires F.D., C1061

  • Investigational Site Number :0320002

    Capital Federal, Buenos Aires, 1012

  • Investigational Site Number :0320003

    Rosario, Santa Fe Province, 2000

  • Investigational Site Number :0320005

    San Miguel de Tucumán, T4000AXL

Other trials in Argentina

Czechia5 sites

  • Investigational Site Number :2030002

    Brno, 65691

  • Investigational Site Number :2030011

    Hradec Králové, 50005

  • Investigational Site Number :2030001

    Jihlava, 58633

  • Investigational Site Number :2030008

    Prague, 10034

  • Investigational Site Number :2030005

    Praha 5 - Motol, 15006

Other trials in Czechia

India5 sites

  • Investigational Site Number :3560005

    Chandigarh, 160012

  • Investigational Site Number :3560007

    Gūrgaon, 122001

  • Investigational Site Number :3560008

    Gūrgaon, 122002

  • Investigational Site Number :3560002

    New Delhi, 110060

  • Investigational Site Number :3560004

    Thiruvananthapuram, 695004

Other trials in India

Israel5 sites

  • Investigational Site Number :3760002

    Ashkelon, 78278

  • Investigational Site Number :3760003

    Haifa, 31096

  • Investigational Site Number :3760006

    Rehovot, 76100

  • Investigational Site Number :3760004

    Safed, 13100

  • Investigational Site Number :3760001

    Tel HaShomer, 52621

Other trials in Israel

Belgium4 sites

  • Investigational Site Number :0560005

    Bruges, B-8000

  • Investigational Site Number :0560004

    Ghent, 9000

  • Investigational Site Number :0560002

    Mons, 7000

  • Investigational Site Number :0560001

    Overpelt, 3900

Other trials in Belgium

Hungary4 sites

  • Investigational Site Number :3480105

    Budapest, 1135

  • Investigational Site Number :3480102

    Budapest, 1145

  • Investigational Site Number :3480106

    Kaposvár, 7400

  • Investigational Site Number :3480103

    Tatabánya, 2800

Other trials in Hungary

South Korea4 sites

  • Investigational Site Number :4100001

    Goyang-si, Gyeonggi-do, 10408

  • Investigational Site Number :4100003

    Seoul, Seoul-teukbyeolsi, 03080

  • Investigational Site Number :4100006

    Seoul, Seoul-teukbyeolsi, 03722

  • Investigational Site Number :4100002

    Seoul, Seoul-teukbyeolsi, 06351

Other trials in South Korea

Brazil3 sites

  • Investigational Site Number :0760002

    Curitiba, 81210-310

  • Investigational Site Number :0760001

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Investigational Site Number :0760007

    São Paulo, 01228-000

Other trials in Brazil

Croatia3 sites

  • Investigational Site Number :1910001

    Zagreb, 10000

  • Investigational Site Number :1910002

    Zagreb, 10000

  • Investigational Site Number :1910003

    Zagreb, 10000

Other trials in Croatia

Slovakia3 sites

  • Investigational Site Number :7030001

    Bratislava, 82606

  • Investigational Site Number :7030002

    Martin, 03659

  • Investigational Site Number :7030004

    Nitra, 950 01

Other trials in Slovakia

Switzerland3 sites

  • Investigational Site Number :7560003

    Aarau, 5001

  • Investigational Site Number :7560002

    Bern, 3010

  • Investigational Site Number :7560004

    Lugano, 6903

Other trials in Switzerland

United Kingdom3 sites

  • Investigational Site Number :8260009

    Bristol, BS10 5NB

  • Investigational Site Number :8260016

    Canterbury, Kent, CT1 3NG

  • Investigational Site Number :8260003

    Exeter, Devon, EX2 5DW

Other trials in United Kingdom

Latvia2 sites

  • Investigational Site Number :4280002

    Riga, LV-1002

  • Investigational Site Number :4280003

    Riga, LV-1005

Other trials in Latvia

Norway2 sites

  • Investigational Site Number :5780002

    Namsos, 7800

  • Investigational Site Number :5780001

    Oslo, 0450

Other trials in Norway

Netherlands1 site

  • Investigational Site Number :5280001

    Amsterdam, 1081 GN

Other trials in Netherlands

Puerto Rico1 site

  • San Juan MS Center-Site Number:8400015

    Guaynabo, 00969

Other trials in Puerto Rico

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 pharmacodynamics (PD) of SAR442168

Read the detailed description

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

Being tested
Tolebrutinib, Teriflunomide HMR1726, 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

  • Teriflunomide HMR1726Drug

    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 NCT04410991
Study groupRoleWhat they receive
SAR442168ExperimentalDose 1 of oral SAR442168 daily + placebo to match the teriflunomide tablet once daily
Receives: Drug: Tolebrutinib; Drug: Placebo to match Teriflunomide
TeriflunomideActive comparatorOral 14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
Receives: Drug: Teriflunomide HMR1726; 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 (12)

  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 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 treatment 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. 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)

  12. 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 start11 Jun 2020
  3. Primary completion16 Jul 2024
  4. Study completion16 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
899 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04410991
Sponsor's protocol ID
EFC16034
Other IDs
U1111-1238-1373, 2020-000644-55
Acronym
GEMINI 2
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 HMR1726 in people with Relapsing Multiple Sclerosis, run by Sanofi at 186 sites in 28 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 186 sites in United States, Spain, France, Russia, Ukraine and 23 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 NCT04410991, 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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