- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03889639
Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis
April 21, 2022 updated by: Sanofi
A Phase 2b Dose-finding Study for SAR442168, a Bruton's Tyrosine Kinase Inhibitor, in Participants With Relapsing Multiple Sclerosis
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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
130
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Gatineau, Canada, J8Y 1W2
- Investigational Site Number 1240002
-
Greenfield Park, Canada, J4V 2J2
- Investigational Site Number 1240001
-
Vancouver, Canada, V6T 2B5
- Investigational Site Number 1240003
-
-
-
-
-
Brno, Czechia, 62500
- Investigational Site Number 2030007
-
Hradec Kralove, Czechia, 50005
- Investigational Site Number 2030004
-
Jihlava, Czechia, 58633
- Investigational Site Number 2030003
-
Ostrava - Poruba, Czechia, 70852
- Investigational Site Number 2030005
-
Pardubice, Czechia, 53203
- Investigational Site Number 2030006
-
Praha 2, Czechia, 12808
- Investigational Site Number 2030001
-
Praha 5 - Motol, Czechia, 15006
- Investigational Site Number 2030002
-
-
-
-
-
Tallinn, Estonia, 11315
- Investigational Site Number 2330001
-
-
-
-
-
Nancy Cedex, France, 54035
- Investigational Site Number 2500004
-
Nantes Cedex 1, France, 44093
- Investigational Site Number 2500001
-
Strasbourg Cedex, France, 67098
- Investigational Site Number 2500002
-
Toulouse Cedex 9, France, 31059
- Investigational Site Number 2500003
-
-
-
-
-
Amsterdam, Netherlands, 1081 HV
- Investigational Site Number 5280001
-
Sittard-Geleen, Netherlands, 6162 BG
- Investigational Site Number 5280002
-
-
-
-
-
Kazan, Russian Federation, 420021
- Investigational Site Number 6430006
-
Moscow, Russian Federation, 125367
- Investigational Site Number 6430003
-
Moscow, Russian Federation, 127015
- Investigational Site Number 6430002
-
Saint-Petersburg, Russian Federation, 197110
- Investigational Site Number 6430001
-
St-Petersburg, Russian Federation, 194044
- Investigational Site Number 6430005
-
St-Petersburg, Russian Federation, 197022
- Investigational Site Number 6430004
-
Tyumen, Russian Federation, 625000
- Investigational Site Number 6430007
-
-
-
-
-
Bratislava, Slovakia, 82606
- Investigational Site Number 7030001
-
Martin, Slovakia, 03659
- Investigational Site Number 7030002
-
-
-
-
-
Barakaldo, Spain, 48903
- Investigational Site Number 7240006
-
Barcelona, Spain, 08035
- Investigational Site Number 7240002
-
Madrid, Spain, 28007
- Investigational Site Number 7240001
-
Murcia, Spain, 30120
- Investigational Site Number 7240004
-
Salt, Spain, 17190
- Investigational Site Number 7240005
-
Sevilla, Spain, 41071
- Investigational Site Number 7240003
-
-
-
-
-
Chernivtsi, Ukraine, 58018
- Investigational Site Number 8040002
-
Dnipro, Ukraine, 49005
- Investigational Site Number 8040005
-
Lviv, Ukraine, 79010
- Investigational Site Number 8040001
-
Lviv, Ukraine, 79013
- Investigational Site Number 8040006
-
Odesa, Ukraine, 65025
- Investigational Site Number 8040009
-
Vinnytsya, Ukraine, 21005
- Investigational Site Number 8040003
-
Zhytomyr, Ukraine, 10002
- Investigational Site Number 8040007
-
-
-
-
Alabama
-
Cullman, Alabama, United States, 35058
- Investigational Site Number 8400005
-
-
Florida
-
Maitland, Florida, United States, 32761
- Investigational Site Number 8400002
-
Sunrise, Florida, United States, 33351
- Investigational Site Number 8400004
-
Tampa, Florida, United States, 33612
- Investigational Site Number 8400009
-
-
Georgia
-
Savannah, Georgia, United States, 31406
- Investigational Site Number 8400007
-
-
Illinois
-
Northbrook, Illinois, United States, 60062
- Investigational Site Number 8400001
-
-
Ohio
-
Dayton, Ohio, United States, 45417
- Investigational Site Number 8400008
-
Westerville, Ohio, United States, 43081
- Investigational Site Number 8400006
-
-
Tennessee
-
Knoxville, Tennessee, United States, 37922
- Investigational Site Number 8400003
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
Experimental: 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.
|
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of new Gd-enhancing T1 hyperintense lesions
Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Number of new Gd-enhancing T1 hyperintense lesions at the end of 12 weeks of SAR442168 treatment as detected by brain MRI
|
Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of new or enlarging T2 lesions
Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Number of new or enlarging T2 lesions at the end of 12 weeks of SAR442168 treatment
|
Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Total number of Gd-enhancing T1 hyperintense lesions
Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Total number of Gd-enhancing T1-hyperintense lesions at the end of 12 weeks of SAR442168 treatment
|
Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8
|
Number of participants experiencing adverse events
Time Frame: From baseline to the end of study (approximately 20 weeks)
|
Number (n) of participants experiencing an adverse event (AE)/Serious Adverse Event (SAE) or potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), or vital signs
|
From baseline to the end of study (approximately 20 weeks)
|
Percentage of participants experiencing adverse events
Time Frame: From baseline to the end of study (approximately 20 weeks)
|
Percentage (%) of participants experiencing an adverse event (AE)/Serious Adverse Event (SAE) or potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), or vital signs
|
From baseline to the end of study (approximately 20 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2019
Primary Completion (Actual)
January 2, 2020
Study Completion (Actual)
January 2, 2020
Study Registration Dates
First Submitted
March 1, 2019
First Submitted That Met QC Criteria
March 23, 2019
First Posted (Actual)
March 26, 2019
Study Record Updates
Last Update Posted (Actual)
April 22, 2022
Last Update Submitted That Met QC Criteria
April 21, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DRI15928
- 2018-003927-12 (EudraCT Number)
- U1111-1220-0572 (Other Identifier: UTN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Relapsing Multiple Sclerosis
-
BiogenWithdrawnRelapsing-Remitting Multiple Sclerosis | Relapsing Forms of Multiple Sclerosis
-
The Cleveland ClinicUniversity Hospitals Cleveland Medical CenterCompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
-
University of California, Los AngelesUnknownRelapsing-remitting Multiple Sclerosis | Secondary-progressive Multiple Sclerosis | Primary-progressive Multiple SclerosisUnited States
-
BiogenAbbVieTerminatedMultiple Sclerosis | Relapsing-Remitting Multiple SclerosisUnited States, Denmark, Italy, United Kingdom, Czechia, Canada, Hungary, Spain, Australia, Israel, Georgia, Serbia, Russian Federation, Ukraine, India, Poland, Brazil, France, Argentina, Germany, Greece, Ireland, Mexico, Moldova, Republic... and more
-
EMD SeronoPfizerCompletedRelapsing-remitting Multiple SclerosisUnited States, United Kingdom, Argentina, Austria, Brazil, France, Germany, Italy, Netherlands, Russian Federation, Spain, Switzerland
-
National Institute of Allergy and Infectious Diseases...Immune Tolerance Network (ITN)CompletedRelapsing-Remitting Multiple SclerosisUnited States
-
BiogenTerminatedRelapsing-Remitting Multiple SclerosisUnited States, Spain, Germany, Australia, Sweden, Czechia, France, Italy, United Kingdom
-
Novartis PharmaceuticalsWithdrawnMultiple Sclerosis (Relapsing Remitting)
-
Genzyme, a Sanofi CompanyTerminatedRelapsing-remitting Multiple SclerosisSweden, Poland, Russian Federation, United States, Canada
-
Novartis PharmaceuticalsCompletedRelapsing-remitting Multiple SclerosisGermany
Clinical Trials on SAR442168
-
SanofiActive, not recruitingRelapsing Multiple SclerosisUnited States, Canada, Czechia, Estonia, France, Netherlands, Russian Federation, Spain, Ukraine
-
SanofiCompleted
-
SanofiCompletedMultiple SclerosisUnited Kingdom
-
SanofiRecruitingPrimary Progressive Multiple SclerosisSpain, Italy, Turkey, India, Israel, Bulgaria, Mexico, Greece, Portugal, United States, Argentina, Australia, Austria, Belarus, Belgium, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, France, Georgia, Germany, Hungary, Japan and more
-
SanofiActive, not recruitingSecondary Progressive Multiple SclerosisUnited States, Argentina, Belgium, Canada, Czechia, France, Germany, Greece, India, Israel, Netherlands, Norway, Portugal, Turkey, United Kingdom, Japan, Austria, Bulgaria, China, Denmark, Finland, Italy, Lithuania, Poland, Romania, Russian... and more
-
Hospital Universitario Dr. Jose E. GonzalezCompletedPernicious Anemia | Megaloblastic Anemia NosMexico
-
Eastern Hepatobiliary Surgery HospitalNot yet recruitingHepatocellular CarcinomaChina
-
SanofiRecruitingRelapsing Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisBelgium
-
SanofiActive, not recruitingRelapsing Multiple SclerosisUnited States, Argentina, Belgium, Brazil, Canada, Chile, Croatia, Czechia, France, Germany, Greece, Hungary, India, Israel, Korea, Republic of, Latvia, Netherlands, Norway, Portugal, Puerto Rico, Russian Federation, Serbia, Slovakia, Spai... and more
-
SanofiActive, not recruitingRelapsing Multiple SclerosisSpain, United States, Mexico, Japan, Austria, Belarus, Bulgaria, Canada, China, Czechia, Denmark, Estonia, Finland, Germany, Italy, Lithuania, Poland, Romania, Russian Federation, Sweden, Taiwan, Turkey, Ukraine, Hong Kong