A Phase 3 interventional study of Tolebrutinib and Teriflunomide HMR1726 in Relapsing Multiple Sclerosis, sponsored by Sanofi. Completed at 186 sites in 28 countries. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2025-07-02.
Sponsored by Sanofi · Phase 3, Interventional, and Treatment
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
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.
Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.
Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
The participant must have at least 1 of the following prior to screening:
Male participants are eligible to participate if they agree to the following during the intervention period and until accelerated elimination procedure:
Plus either:
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 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.
Exclusion criteria:
The participant has conditions or situations that would adversely affect participation in this study, including but not limited to:
The participant has any of the following:
Dose 1 of oral SAR442168 daily + placebo to match the teriflunomide tablet once daily
Drug: Tolebrutinib · Drug: Placebo to match Teriflunomide
Oral 14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
Drug: Teriflunomide HMR1726 · Drug: Placebo to match Tolebrutinib
Pharmaceutical form: Tablet Route of administration: Oral
Also known as: SAR442168
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Tablet Route of administration: Oral
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Baseline (Day 1) to EOS (up to approximately 48 months)
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.
Time frame: Baseline (Day 1) to EOS (up to approximately 48 months)
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.
Time frame: Baseline (Day 1) to approximately 48 months
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.
Time frame: Month 6 to EOS (up to approximately 48 months)
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.
Time frame: Baseline (Day 1) to EOS (up to approximately 48 months)
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.
Time frame: 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
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.
Time frame: Baseline (Day 1) to EOS (up to approximately 48 months)
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.
Time frame: Baseline (Day 1) to EOS (up to approximately 48 months)
This study was conducted at 154 sites in 25 countries. A total of 1093 participants were screened from 11-Jun-2020 to 08-Aug-2022, of which 194 were screen failures. Screen failures were mainly due to not meeting eligibility criteria.
| Milestone | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Started | 452 | 447 |
| Randomized and treated | 451 | 447 |
| Completed | 378 | 384 |
| Not completed | 74 | 63 |
| Withdrew: Poor compliance to protocol | 5 | 4 |
| Withdrew: Withdrawal by subject | 59 | 55 |
| Withdrew: Other | 10 | 4 |
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.
| relapses per participant year | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses | 0.109 (0.088 to 0.134) | 0.108 (0.089 to 0.131) |
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.
| months | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Time to Onset of 6-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale | 12.14 (1.4 to 38.9) | 15.12 (2.0 to 37.1) |
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.
| months | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Time to Onset of 3-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale | 12.11 (1.4 to 39.1) | 12.11 (2.0 to 42.1) |
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.
| number of new and/or enlarging T2lesions | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Mean Number of New and/or Enlarging T2-Hyperintense Lesions Per Year | 4.369 (3.587 to 5.322) | 5.092 (4.340 to 5.975) |
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.
| number of new Gd-enhancing T1 lesions | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Mean Number of New Gadolinium-Enhancing T1-Hyperintense Lesions Per Scan | 0.217 (0.169 to 0.280) | 0.460 (0.365 to 0.581) |
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.
| score on a scale | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Change From Baseline in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT) at EOS | 0.428 ± 0.0373 | 0.374 ± 0.0370 |
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.
| T-score | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test Second Edition (CVLT-II) at EOS | 16.431 ± 0.6825 | 15.819 ± 0.6740 |
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.
| months | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Time to Onset of 6-Month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale | 12.05 (2.8 to 30.6) | 9.04 (2.6 to 33.5) |
MRI of the brain was performed at the specified timepoints to detect the changes in brain volume loss.
| percent change | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Percent Change in Brain Volume Loss at EOS Compared to Month 6 | -0.740 ± 0.0394 | -0.696 ± 0.0387 |
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.
| score on a scale | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Physical health composite score | -1.040 ± 0.7404 | -1.199 ± 0.7304 |
| Mental health composite score | -1.657 ± 0.8709 | -1.390 ± 0.8581 |
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.
| Participants | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| TEAEs | 387 | 385 |
| TESAEs | 37 | 49 |
| TEAEs leading to permanent study intervention discontinuation | 17 | 19 |
| TEAESIs | 40 | 46 |
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.
| picogram/milliliter | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| NfL | -0.900 (-4.390 to 0.770) | -0.150 (-3.560 to 2.750) |
| Chi3L1 | -281.100 (-6148.400 to 5647.000) | 1462.500 (-4578.600 to 7002.700) |
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.
| gram per liter | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| IgG | -0.590 (-1.330 to 0.230) | 0.140 (-0.720 to 1.060) |
| IgM | -0.160 (-0.320 to -0.020) | -0.320 (-0.530 to -0.150) |
Collected over 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. Deaths were collected from baseline (Day 1) up to end of follow-up, approximately 48 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Teriflunomide 14 mg | 2/452 (0.4%) | 37/451 (8.2%) | 313/451 (69.4%) |
| Tolebrutinib 60 mg | 1/447 (0.2%) | 49/447 (11%) | 279/447 (62.4%) |
| Event | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Suicide AttemptPsychiatric disorders | 0/451 | 4/447 |
| AppendicitisInfections and infestations | 3/451 | 1/447 |
| GastroenteritisInfections and infestations | 3/451 | 0/447 |
| Covid-19Infections and infestations | 1/451 | 2/447 |
| Covid-19 PneumoniaInfections and infestations | 0/451 | 2/447 |
| Uterine LeiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/451 | 2/447 |
| Relapsing-Remitting Multiple SclerosisNervous system disorders | 0/451 | 2/447 |
| Escherichia PyelonephritisInfections and infestations | 2/451 | 0/447 |
| Breast CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/451 | 1/447 |
| Acute SinusitisInfections and infestations | 0/451 | 1/447 |
| Event | Teriflunomide 14 mg | Tolebrutinib 60 mg |
|---|---|---|
| Covid-19Infections and infestations | 115/451 | 106/447 |
| AlopeciaSkin and subcutaneous tissue disorders | 73/451 | 37/447 |
| NasopharyngitisInfections and infestations | 64/451 | 60/447 |
| HeadacheNervous system disorders | 54/451 | 61/447 |
| DiarrhoeaGastrointestinal disorders | 49/451 | 22/447 |
| Upper Respiratory Tract InfectionInfections and infestations | 36/451 | 31/447 |
| NeutropeniaBlood and lymphatic system disorders | 34/451 | 10/447 |
| HypertensionVascular disorders | 34/451 | 13/447 |
| FatigueGeneral disorders | 21/451 | 30/447 |
| Urinary Tract InfectionInfections and infestations | 30/451 | 25/447 |
Analysis was performed on the randomized population.
| Age, Continuous(years) | Teriflunomide 14 mg | Tolebrutinib 60 mg | Total |
|---|---|---|---|
| Mean | 36.1 ± 9.3 | 36.6 ± 9.3 | 36.4 ± 9.3 |
| Sex: Female, Male(Participants) | Teriflunomide 14 mg | Tolebrutinib 60 mg | Total |
|---|---|---|---|
| Female | 293 | 300 | 593 |
| Male | 159 | 147 | 306 |
| Race (NIH/OMB)(Participants) | Teriflunomide 14 mg | Tolebrutinib 60 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 19 | 23 | 42 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 11 | 7 | 18 |
| White | 417 | 411 | 828 |
| More than one race | 3 | 3 | 6 |
| Unknown or Not Reported | 2 | 3 | 5 |
Showing the first 100 of 186 sites across 28 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: 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
This study is completed, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Sanofi