9 trials tracked · 1 active · last refreshed 2026-08-10
Tolebrutinib (Sanofi) was the first BTK inhibitor to report positive Phase III results in MS — specifically in non-relapsing secondary progressive MS, a harder-to-treat, later stage of the disease where most existing drugs (built for relapsing MS) don't work well. That completed trial was a notable result for the field: one of the first therapies to show any benefit in progressive MS without relapses.
Most of its other trials are now completed rather than active — companion Phase III trials in relapsing and primary progressive MS, and several standard pharmacology studies. Its one still-active trial is a long-term safety extension, the stage a drug typically reaches after its efficacy trials have already read out.
Click a row for what it's testing, where, and how many participants.
| NCT ID | Title | Phase | Status | Started | |
|---|---|---|---|---|---|
| ▸ | NCT06372145 | A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis. | Phase III | Active, not recruiting | 2024-04-16 |
This is a Phase 3 extension, global, multicenter study to assess the long-term safety and tolerability of tolebrutinib in adult participants (aged ≥18 years) with RMS, PPMS, or NRSPMS who were previously enrolled in the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 tolebrutinib pivotal trials (GEMINI 1 \[EFC16033\], GEMINI 2 \[EFC16034\], HERCULES \[EFC16645\], or PERSEUS \[EFC16035\]). SUBSTUDY: ToleDYNAMIC substudy Enrollment 2,500 (estimated) Sites 352 across 47 countries Countries Argentina, Australia, Austria, Belgium, Brazil +42 more Sponsor Sanofi Primary outcome: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs leading to permanent study intervention discontinuation | |||||
| ▸ | NCT04742400 | Tolebrutinib, a Brain-penetrant Bruton's Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis | Phase II | Unknown | 2021-04-15 |
Background: Some multiple sclerosis (MS) lesions stay inflamed for very long periods of time. This type of inflammation is not affected by any MS medications. These lesions can lead to slow worsening of MS symptoms. Researchers want to see if a new drug can help. Objective: To see if tolebrutinib can help clear inflammation in MS brain lesions. Eligibility: Adults ages 18 and older with MS who are on an anti-CD20 therapy. Design: Participants will be screened under protocol #89-N-0045. Participants will have a medical history. They will have physical and neurological exams. They will have blood and urine tests. The progression of their MS will be assessed. Participants will have MRIs of the brain. The MRI scanner is shaped like a cylinder. It uses a magnetic field and radio waves to take pictures of the body. During the MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. Participants may have electrocardiograms to measure the heart s electrical activity. Participants may have lumbar punctures ( spinal taps ). A small needle will be inserted into the spinal canal in the lower back. Fluid will be collected. Some participants will take tolebrutinib pills by mouth once a day for at least 96 weeks. They will stop their anti-CD20 therapy. They will have at least 10 study visits. Some participants will not take tolebrutinib. They will stay on their anti-CD20 therapy. They will have 5 study visits. Participation will last at least 96 weeks. Enrollment 12 (actual) Sites 1 across 1 country Countries United States Sponsor National Institute of Neurological Disorders and Stroke (NINDS) Primary outcome: Disappearance of Paramagnetic Rim Lesions at 48 Weeks of 60 mg of Tolebrutinib. | |||||
| ▸ | NCT04411641 | Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (HERCULES) | Phase III | Completed | 2020-09-24 |
Primary Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS Secondary Objective: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168 Enrollment 1,131 (actual) Sites 306 across 31 countries Countries Argentina, Australia, Austria, Belarus, Belgium +26 more Sponsor Sanofi Primary outcome: Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS) | |||||
| ▸ | NCT04458051 | Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) | Phase III | Completed | 2020-08-13 |
Primary Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in primary progressive multiple sclerosis (PPMS) Secondary Objectives: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 in PPMS and its relationship to efficacy and safety To evaluate pharmacodynamics of SAR442168 Enrollment 767 (actual) Sites 277 across 42 countries Countries Argentina, Australia, Austria, Belarus, Belgium +37 more Sponsor Sanofi Primary outcome: 6-month composite Confirmed Disability Progression (cCDP) | |||||
| ▸ | NCT06106074 | Study of the Tolerability and Pharmacokinetics of Oral Doses of SAR442168 With a Food Effect Investigation in Healthy Adult Participants | Phase I | Completed | 2020-08-10 |
This is a randomized, placebo-controlled, four-part, Phase I, first in human (FIH) study to assess the tolerability and pharmacokinetics (PK) of ascending single and 14-day repeated oral doses of SAR442168 with a food effect investigation in healthy adult participants. * In Part 1a: The tolerability and safety of SAR442168 and the pharmacokinetic parameters of SAR442168 and metabolite(s)after ascending single oral doses in fasted and fed conditions * In Part 1b: The relationship of PK of SAR442168 and metabolite(s) in cerebrospinal fluid (CSF) to that in plasma after single oral doses given in fed conditions (moderate-fat meal) * In Part 1c: The effect of a high-fat meal on the pharmacokinetics of SAR442168 and metabolite(s) (high-fat) * In Part 1d: The effect of a high-fat meal on the pharmacokinetics of SAR442168 and metabolite(s) (standardized high-fat meal) * In Part 2: The tolerability and safety of SAR442168 and the pharmacokinetic parameters of SAR442168 and metabolite(s) after 14-day ascending repeated oral doses of SAR442168 given in fed conditions (moderate-fat meal). Enrollment 71 (actual) Sites 1 across 1 country Countries United States Sponsor Sanofi Primary outcome: Part 1a and Part 2: Number of participants with Adverse Events (AEs) and treatment-emergent adverse events (TEAEs) | |||||
| ▸ | NCT04410978 | Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1) | Phase III | Completed | 2020-06-30 |
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 Enrollment 974 (actual) Sites 179 across 24 countries Countries Austria, Belarus, Bulgaria, Canada, China +19 more Sponsor Sanofi Primary outcome: Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses | |||||
| ▸ | NCT04410991 | Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2) | Phase III | Completed | 2020-06-11 |
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 Enrollment 899 (actual) Sites 186 across 28 countries Countries Argentina, Belgium, Brazil, Canada, Chile +23 more Sponsor Sanofi Primary outcome: Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses | |||||
| ▸ | NCT06064539 | Study of Drug-drug Interaction of the Effects of Gemfibrozil and Rifampicin on SAR442168 in Healthy Adult Subjects | Phase I | Completed | 2020-05-18 |
This is a Phase 1, single-center, open-label, non-randomized study to assess the effects of CYP2C8 inhibition using gemfibrozil, and CYP3A4 and CYP2C8 induction using rifampicin on the pharmacokinetics of SAR442168 in healthy male participants aged 18 to 45 years. Enrollment 30 (actual) Sites 1 across 1 country Countries United States Sponsor Sanofi Primary outcome: Pharmacokinetics: AUClast of SAR442168 | |||||
| ▸ | NCT03996291 | Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis | Phase II | Completed | 2019-09-23 |
Primary Objective: To determine the long-term safety and tolerability of SAR442168 in RMS participants Secondary Objective: To evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods Enrollment 125 (actual) Sites 37 across 9 countries Countries Canada, Czechia, Estonia, France, Netherlands +4 more Sponsor Sanofi Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | |||||
This page is regenerated from ClinicalTrials.gov data and summarized once per refresh — nothing here is generated live when you visit. For informational purposes only; not medical advice.