Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis

NCT ID: NCT03889639

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-29
• Study Completion Date: 2020-01-02

Brief Summary

Primary Objective:

To determine the dose-response relationship for SAR442168 to reduce the number of new active brain lesions.

Secondary Objectives:

• To evaluate efficacy of SAR442168 on disease activity as assessed by imaging measures.
• To evaluate the safety and tolerability of SAR442168.

Detailed Description

The total study duration was 24 weeks which included a screening period of 4 weeks, a treatment period of 16 weeks, and a follow-up period of up to 4 weeks. Participants who completed the Week 16 visit were proposed to be enrolled in a long-term extension safety and efficacy study to assess safety, tolerability and efficacy of SAR442168.

Conditions

Relapsing Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1: SAR442168 5 mg Then Placebo

Participants received SAR442168 5 milligrams (mg), orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 1: SAR442168 15 mg Then Placebo

Participants received SAR442168 15 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 1: SAR442168 30 mg Then Placebo

Participants received SAR442168 30 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 1: SAR442168 60 mg Then Placebo

Participants received SAR442168 60 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 2: Placebo Then SAR442168 5 mg

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 5 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 2: Placebo Then SAR442168 15 mg

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 15 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 2: Placebo Then SAR442168 30 mg

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 30 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cohort 2: Placebo Then SAR442168 60 mg

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 60 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Group Type: EXPERIMENTAL

SAR442168

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Interventions

SAR442168

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: Film coated tablet; Route of administration: Oral

Intervention Type: DRUG

Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent.
• Participant was diagnosed with relapsing multiple sclerosis (RMS) according to the 2017 revision of the McDonald diagnostic criteria.
• Participant must had at least 1 documented relapse within the previous year, OR greater than or equal to (>=) 2 documented relapses within the previous 2 years, OR >=1 active Gadolinium (Gd) enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
• A female participant must had used a double contraception method including a highly effective method of birth control from inclusion and up to 2 months after the last study dose, except if she had undergone sterilization at least 3 months earlier or was postmenopausal. Menopause was defined as being amenorrheic for >=12 months with serum follicle-stimulating hormone (FSH) level greater than (>) 30 International Units per liters.
• Male participants, whose partners were of childbearing potential (including breastfeeding women), must had accepted to use, during sexual intercourse, a double contraceptive method according to the following algorithm: (condom) plus (intrauterine device or hormonal contraceptive) from inclusion up to 3 months after the last dose.
• Male participants whose partners were pregnant must had used, during sexual intercourse, a condom from inclusion up to 3 months after the last dose.
• Male participants had agreed not to donate sperm from the inclusion up to 3 months after the last dose.
• Participant had given written informed consent prior to undertaking any study-related procedure.

Exclusion Criteria

• The participant had been diagnosed with primary progressive multiple sclerosis according to the 2017 revision of the McDonald diagnostic criteria or with non relapsing secondary progressive multiple sclerosis.
• Requirement for concomitant treatment that could bias the primary evaluation.
• Contraindication for MRI.
• Contraindications to use MRI Gd contrast-enhancing preparations.
• History of infection with the human immunodeficiency virus (HIV).
• History of active or latent tuberculosis.
• Any other active infections that would adversely affect participation or investigational medicinal product administration in this study, as judged by the Investigator.
• Presence of any screening laboratory or electrocardiogram values outside normal limits that were considered in the Investigator's judgment to be clinically significant.
• Presence of liver injury.
• At screening, the participant was positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or was positive for hepatitis C antibody.
• Bleeding disorder or known platelet dysfunction at any time prior to screening visit.
• Participant had received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) within 2 months before first treatment visit.
• Participant was receiving strong inducers or inhibitors of cytochrome P450 3A (CYP3A) or CYP2C8 hepatic enzymes.
• Participant was receiving anticoagulant/antiplatelet therapies.
• Participant had taken other investigational drugs within 3 months or 5 half lives, whichever was longer, before screening visit.
• Participant had an Expanded Disability Status Scale score >5.5 at first screening visit.
• Participant had a relapse in the 30 days prior to randomization.
• Participant was pregnant or a breastfeeding woman.
• History or presence of significant other concomitant illness.
• The participant had received medications/treatments for multiple sclerosis within a specified time frame.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400005

Cullman, Alabama, United States

Investigational Site Number 8400002

Maitland, Florida, United States

Investigational Site Number 8400004

Sunrise, Florida, United States

Investigational Site Number 8400009

Tampa, Florida, United States

Investigational Site Number 8400007

Savannah, Georgia, United States

Investigational Site Number 8400001

Northbrook, Illinois, United States

Investigational Site Number 8400008

Dayton, Ohio, United States

Investigational Site Number 8400006

Westerville, Ohio, United States

Investigational Site Number 8400003

Knoxville, Tennessee, United States

Investigational Site Number 1240002

Gatineau, , Canada

Investigational Site Number 1240001

Greenfield Park, , Canada

Investigational Site Number 1240003

Vancouver, , Canada

Investigational Site Number 2030007

Brno, , Czechia

Investigational Site Number 2030004

Hradec Králové, , Czechia

Investigational Site Number 2030003

Jihlava, , Czechia

Investigational Site Number 2030005

Ostrava - Poruba, , Czechia

Investigational Site Number 2030006

Pardubice, , Czechia

Investigational Site Number 2030001

Prague, , Czechia

Investigational Site Number 2030002

Praha 5 - Motol, , Czechia

Investigational Site Number 2330001

Tallinn, , Estonia

Investigational Site Number 2500004

Nancy, , France

Investigational Site Number 2500001

Nantes, , France

Investigational Site Number 2500002

Strasbourg, , France

Investigational Site Number 2500003

Toulouse, , France

Investigational Site Number 5280001

Amsterdam, , Netherlands

Investigational Site Number 5280002

Sittard-Geleen, , Netherlands

Investigational Site Number 6430006

Kazan', , Russia

Investigational Site Number 6430003

Moscow, , Russia

Investigational Site Number 6430002

Moscow, , Russia

Investigational Site Number 6430005

Saint Petersburg, , Russia

Investigational Site Number 6430004

Saint Petersburg, , Russia

Investigational Site Number 6430001

Saint Petersburg, , Russia

Investigational Site Number 6430007

Tyumen, , Russia

Investigational Site Number 7030001

Bratislava, , Slovakia

Investigational Site Number 7030002

Martin, , Slovakia

Investigational Site Number 7240006

Barakaldo, , Spain

Investigational Site Number 7240002

Barcelona, , Spain

Investigational Site Number 7240001

Madrid, , Spain

Investigational Site Number 7240004

Murcia, , Spain

Investigational Site Number 7240005

Salt, , Spain

Investigational Site Number 7240003

Seville, , Spain

Investigational Site Number 8040002

Chernivtsi, , Ukraine

Investigational Site Number 8040005

Dnipro, , Ukraine

Investigational Site Number 8040001

Lviv, , Ukraine

Investigational Site Number 8040006

Lviv, , Ukraine

Investigational Site Number 8040009

Odesa, , Ukraine

Investigational Site Number 8040003

Vinnytsia, , Ukraine

Investigational Site Number 8040007

Zhytomyr, , Ukraine

Countries

United States; Canada; Czechia; Estonia; France; Netherlands; Russia; Slovakia; Spain; Ukraine

References

Reich DS, Arnold DL, Vermersch P, Bar-Or A, Fox RJ, Matta A, Turner T, Wallstrom E, Zhang X, Mares M, Khabirov FA, Traboulsee A; Tolebrutinib Phase 2b Study Group. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021 Sep;20(9):729-738. doi: 10.1016/S1474-4422(21)00237-4.

Reference Type: DERIVED

PMID: 34418400 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25224&tenant=MT_SNY_9011

DRI15928 Plain Language Results Summary

Other Identifiers

2018-003927-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1220-0572

Identifier Type: OTHER

Identifier Source: secondary_id

DRI15928

Identifier Type: -

Identifier Source: org_study_id