Dose-finding Study for SAR442168 in Relapsing Multiple Sc... | NCT03889639 | Trialant
NCT03889639
Sponsor
Sanofi
Status
Completed
Last Update Posted
Sep 17, 2025Actual
Enrollment
130Actual
Phase
Phase 2
Conditions
Relapsing Multiple Sclerosis
Interventions
SAR442168
Placebo
Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Countries
United States
Canada
Czechia
Estonia
France
Netherlands
Russia
Slovakia
Spain
Ukraine
Protocol Section
Identification Module
NCT ID
NCT03889639
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
DRI15928
Secondary IDs
ID
Type
Description
Link
2018-003927-12
EudraCT Number
U1111-1220-0572
Other Identifier
UTN
Brief Title
Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis
Official Title
A Phase 2b Dose-finding Study for SAR442168, a Bruton's Tyrosine Kinase Inhibitor, in Participants With Relapsing Multiple Sclerosis
Acronym
Not provided
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Sep 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 29, 2019Actual
Primary Completion Date
Jan 2, 2020Actual
Completion Date
Jan 2, 2020Actual
First Submitted Date
Mar 1, 2019
First Submission Date that Met QC Criteria
Mar 23, 2019
First Posted Date
Mar 26, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Dec 7, 2022
Results First Submitted that Met QC Criteria
Mar 7, 2023
Results First Posted Date
Mar 8, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 19, 2021
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Mar 8, 2023Actual
Last Update Submitted Date
Sep 16, 2025
Last Update Posted Date
Sep 17, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
SanofiINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 Module
Conditions
Relapsing Multiple Sclerosis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
130Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1: SAR442168 5 mg Then Placebo
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 1: SAR442168 15 mg Then Placebo
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 1: SAR442168 30 mg Then Placebo
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
SAR442168
Drug
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Cohort 1: SAR442168 15 mg Then Placebo
Cohort 1: SAR442168 30 mg Then Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions
Number of new Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants). Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to collected during placebo administration in Cohort 1 (Weeks 12 to 16).
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants) and at Week 4 for Cohort 2 placebo
Secondary Outcomes
Measure
Description
Time Frame
Number of New or Enlarging T2 Lesions
Number of new and enlarging T2 lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo
Other Outcomes
Not provided
Eligibility Module
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.
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.
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
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
A total of 130 participants were randomized and treated in this study. Participants were centrally assigned to 1 of 8 arms (4 dose groups at an equal ratio to start with SAR442168 [all considered as Cohort 1] or placebo [all considered as Cohort 2]).
Recruitment Details
The study was conducted at 44 active centers in 10 countries. A total of 168 participants were screened from 29-March-2019 to 29-August-2019, of which 38 participants were screen failures. Screen failures were mainly due to selection criteria not met.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 9, 2019
Dec 7, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Sweden
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Cohort 1: SAR442168 60 mg Then Placebo
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 2: Placebo Then SAR442168 5 mg
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 2: Placebo Then SAR442168 15 mg
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 2: Placebo Then SAR442168 30 mg
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 2: Placebo Then SAR442168 60 mg
Experimental
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.
Drug: SAR442168
Drug: Placebo
Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Cohort 1: SAR442168 5 mg Then Placebo
Cohort 1: SAR442168 60 mg Then Placebo
Cohort 2: Placebo Then SAR442168 15 mg
Cohort 2: Placebo Then SAR442168 30 mg
Cohort 2: Placebo Then SAR442168 5 mg
Cohort 2: Placebo Then SAR442168 60 mg
Placebo
Drug
Pharmaceutical form: Film coated tablet; Route of administration: Oral
Cohort 1: SAR442168 15 mg Then Placebo
Cohort 1: SAR442168 30 mg Then Placebo
Cohort 1: SAR442168 5 mg Then Placebo
Cohort 1: SAR442168 60 mg Then Placebo
Cohort 2: Placebo Then SAR442168 15 mg
Cohort 2: Placebo Then SAR442168 30 mg
Cohort 2: Placebo Then SAR442168 5 mg
Cohort 2: Placebo Then SAR442168 60 mg
Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Drug
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
Cohort 1: SAR442168 15 mg Then Placebo
Cohort 1: SAR442168 30 mg Then Placebo
Cohort 1: SAR442168 5 mg Then Placebo
Cohort 1: SAR442168 60 mg Then Placebo
Cohort 2: Placebo Then SAR442168 15 mg
Cohort 2: Placebo Then SAR442168 30 mg
Cohort 2: Placebo Then SAR442168 5 mg
Cohort 2: Placebo Then SAR442168 60 mg
Total Number of Gd-enhancing T1-hyperintense Lesions
Total number of Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period
Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with use of study drug. Serious AE (SAE) was defined as any untoward medical occurrence that, at any dose resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs were defined as AEs (serious/non-serious) that developed, worsened, or became serious during on-treatment period (for this outcome measure- "Weeks 1 to 4 period": time from 1st administration of study drug to Week 4). Cohorts 1 and 2 received SAR442168 and placebo for first 4 weeks, respectively.
From Baseline up to Week 4
Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period
AE was defined as any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug. SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs: AEs that developed, worsened, or became serious during on-treatment period (for this outcome measure defined as "SAR442168 treatment period" which was considered as Weeks 1 to 12 for Cohort 1 and Weeks 4 to 16 for Cohort 2).
Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants
Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG)
Individual clinically relevant abnormalities was defined as potentially clinically significant abnormalities (PCSA) considered as SAEs or TEAEs leading to study treatment discontinuation or study discontinuation during the on-treatment period (time from first study drug administration until Week 16), considering all evaluations performed during the on-treatment period that included unscheduled or repeated evaluations.
Baseline up to Week 12 for Cohort 1 participants; Baseline up to Week 4 for Cohort 2 Placebo and from Weeks 4 to 16 for Cohort 2 SAR442168 receiving participants
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.
FG002
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.
FG003
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.
FG004
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.
FG005
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.
FG006
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.
FG007
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.
FG00016 subjects
FG00116 subjects
FG00216 subjects
FG00316 subjects
FG00417 subjects
FG00516 subjects
FG00617 subjects
FG00716 subjects
COMPLETED
FG00016 subjects
FG00116 subjects
FG00216 subjects
FG00316 subjects
FG00417 subjects
FG00516 subjects
FG00617 subjects
FG00715 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0071 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0071 subjects
Baseline analysis was performed on randomized population that included any participant who had been allocated to a randomly assigned treatment, regardless of whether the treatment kit was used.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1: SAR442168 5 mg Then Placebo
Participants received SAR442168 5 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.
BG001
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.
BG002
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.
BG003
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.
BG004
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.
BG005
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.
BG006
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.
BG007
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.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00016
BG00116
BG00216
BG00316
BG00417
BG00516
BG00617
BG00716
BG008130
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00037.4± 11.1
BG00135.1± 7.9
BG00240.8± 8.7
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0009
BG00110
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions
Number of new Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants). Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to collected during placebo administration in Cohort 1 (Weeks 12 to 16).
Analysis was performed on modified intent-to-treat (mITT) population that included all randomly assigned participants exposed to the study drug, analyzed according to the treatment assigned by randomization. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
lesions
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants) and at Week 4 for Cohort 2 placebo
ID
Title
Description
OG000
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
OG001
Cohorts 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG002
Cohorts 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG003
Cohorts 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG004
Cohorts 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Units
Counts
Participants
OG00059
OG00131
OG00231
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.03± 2.50
OG0011.39± 3.20
OG0020.77± 1.48
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
SAR442168 5 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.1673
Relative reduction in lesions
-56.16
2-Sided
95
-193.99
17.05
Superiority
Relative reduction in lesions in SAR442168 5 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95 percentage (%) confidence interval (CI) were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
Secondary
Number of New or Enlarging T2 Lesions
Number of new and enlarging T2 lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
Analysis was performed on mITT population. Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to be collected during placebo administration in Cohort 1 (Week 12 to 16). Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
lesions
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo
ID
Title
Description
OG000
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
OG001
Cohorts 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG002
Secondary
Total Number of Gd-enhancing T1-hyperintense Lesions
Total number of Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
Analysis was performed on mITT population. Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to be collected during placebo administration in Cohort 1 (Weeks 12 to 16). Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
lesions
After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo
ID
Title
Description
OG000
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
OG001
Cohorts 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG002
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period
Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with use of study drug. Serious AE (SAE) was defined as any untoward medical occurrence that, at any dose resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs were defined as AEs (serious/non-serious) that developed, worsened, or became serious during on-treatment period (for this outcome measure- "Weeks 1 to 4 period": time from 1st administration of study drug to Week 4). Cohorts 1 and 2 received SAR442168 and placebo for first 4 weeks, respectively.
Analysis was performed on safety population that included all participants from randomized population who had received at least 1 dose or part of dose of study drug. Data was planned to be collected and analyzed on participants at each dose level of SAR442168 in Cohort 1 and pooled population of participants receiving Placebo in Cohort 2 and not planned to be collected during Cohort 1 Placebo administration (Weeks 12 to 16).
Posted
Count of Participants
Participants
From Baseline up to Week 4
ID
Title
Description
OG000
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
OG001
Cohort 1: SAR442168 5 mg
Secondary
Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period
AE was defined as any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug. SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs: AEs that developed, worsened, or became serious during on-treatment period (for this outcome measure defined as "SAR442168 treatment period" which was considered as Weeks 1 to 12 for Cohort 1 and Weeks 4 to 16 for Cohort 2).
Analysis was performed on safety population. Data was planned to be collected and analyzed on pooled participants at each dose level of SAR442168 (either in Cohort 1 or 2), and was not planned to be collected during placebo administration in either Cohort 1 or 2.
Posted
Count of Participants
Participants
Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants
ID
Title
Description
OG000
Cohorts 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG001
Cohorts 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Secondary
Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG)
Individual clinically relevant abnormalities was defined as potentially clinically significant abnormalities (PCSA) considered as SAEs or TEAEs leading to study treatment discontinuation or study discontinuation during the on-treatment period (time from first study drug administration until Week 16), considering all evaluations performed during the on-treatment period that included unscheduled or repeated evaluations.
Analysis was performed on safety population. Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 or 2), and pooled population of participants receiving Placebo in Cohort 2 and was not planned to be collected during placebo administration in Cohort 1 (Weeks 12 to 16).
Posted
Count of Participants
Participants
Baseline up to Week 12 for Cohort 1 participants; Baseline up to Week 4 for Cohort 2 Placebo and from Weeks 4 to 16 for Cohort 2 SAR442168 receiving participants
ID
Title
Description
OG000
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
OG001
Cohorts 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Time Frame
All AEs were collected from the first dose of study drug until the end of the study (Week 16) regardless of seriousness or relationship to study drug
Description
Reported AEs are TEAEs that developed, worsened, or became serious during the treatment-emergent period (time from the first dose of study treatment until the last study visit). Analysis was performed on safety population. Data is reported for pooled populations of Cohort 1 and 2 for each dose of study drug, i.e., events during the 12 weeks of SAR442168 treatment, and for all participants who received placebo either in Cohort 1 or 2 during the placebo treatment period.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1 and 2: SAR442168 5 mg
All participants who received SAR442168 5 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
0
33
0
33
19
33
EG001
Cohort 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
0
32
0
32
17
32
EG002
Cohort 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
0
33
0
33
18
33
EG003
Cohort 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
0
32
1
32
16
32
EG004
Cohort 1: Pooled Placebo
All participants in Cohort 1 who received placebo matching to SAR442168 orally once daily in Weeks 12-16 during the 16 weeks treatment period.
0
64
0
64
10
64
EG005
Cohort 2: Pooled Placebo
All participants in Cohort 2 who received placebo matching to SAR442168 orally once daily for first 4 weeks during the 16 weeks treatment period.
0
66
0
66
23
66
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Multiple Sclerosis Relapse
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG0031 events1 affected32 at risk
EG0040 events0 affected64 at risk
EG0050 events0 affected66 at risk
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Bronchitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG0030 events0 affected32 at risk
EG0040 events0 affected64 at risk
EG0050 events0 affected66 at risk
Gastroenteritis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Herpes Zoster
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Influenza
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Oral Herpes
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Respiratory Tract Infection
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Respiratory Tract Infection Viral
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0012 events2 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG0012 events2 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Viral Upper Respiratory Tract Infection
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Vulvovaginal Candidiasis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Allergy To Animal
Immune system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Depression
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Grief Reaction
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Irritability
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Headache
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0003 events1 affected33 at risk
EG0013 events3 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Hypersomnia
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Migraine
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Migraine Without Aura
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Muscle Spasticity
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Restless Legs Syndrome
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Syncope
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Tension Headache
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Dry Eye
Eye disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Eye Pain
Eye disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Atrioventricular Block First Degree
Cardiac disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Sinus Bradycardia
Cardiac disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Supraventricular Extrasystoles
Cardiac disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Hot Flush
Vascular disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Sinus Pain
Respiratory, thoracic and mediastinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Upper Respiratory Tract Inflammation
Respiratory, thoracic and mediastinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Chronic Gastritis
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Dental Caries
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0012 events2 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0011 events1 affected32 at risk
EG0022 events2 affected33 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Intervertebral Disc Degeneration
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Muscle Spasms
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Muscle Twitching
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Pain In Extremity
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Calculus Urinary
Renal and urinary disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Renal Colic
Renal and urinary disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Urinary Incontinence
Renal and urinary disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Urinary Tract Inflammation
Renal and urinary disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Cervix Inflammation
Reproductive system and breast disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 22.1
Systematic Assessment
EG0002 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Premenstrual Headache
Reproductive system and breast disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Uterine Polyp
Reproductive system and breast disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Cystic Lymphangioma
Congenital, familial and genetic disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Chronic Fatigue Syndrome
General disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Fatigue
General disorders
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Injection Site Erythema
General disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Oedema Peripheral
General disorders
MedDRA 22.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Pain
General disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Pyrexia
General disorders
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDRA 22.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Aspartate Aminotransferase Increased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Blood Glucose Increased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Blood Immunoglobulin M Decreased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Glomerular Filtration Rate Decreased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Red Blood Cell Count Decreased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Reticulocyte Count Decreased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Weight Increased
Investigations
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Accidental Overdose
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Animal Bite
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Arthropod Sting
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected32 at risk
EG0020 events0 affected33 at risk
EG003
Rib Fracture
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected32 at risk
EG0021 events1 affected33 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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Relative reduction in lesions in SAR442168 15 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
OG000
OG003
SAR442168 30 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.7674
Relative reduction in lesions
13.49
2-Sided
95
-126.05
66.89
Superiority
Relative reduction in lesions in SAR442168 30 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
OG000
OG004
SAR442168 60 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.0178
Relative reduction in lesions
85.02
2-Sided
95
28.02
96.88
Superiority
Relative reduction in lesions in SAR442168 60 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
Cohorts 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG003
Cohorts 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG004
Cohorts 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Units
Counts
Participants
OG00059
OG00131
OG00231
OG00333
OG00431
Title
Denominators
Categories
Title
Measurements
OG0002.12± 5.16
OG0011.90± 3.97
OG0021.32± 1.83
OG0031.30± 4.90
OG0040.23± 0.62
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
SAR442168 5 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.7736
Relative reduction in lesions
10.17
2-Sided
95
-86.49
56.73
Superiority
Relative reduction in lesions in SAR442168 5 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model without adjusting for Baseline T2 lesion activity as all participants had at least one T2 lesion at Baseline.
OG000
OG002
SAR442168 15 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.2480
Relative reduction in lesions
37.07
2-Sided
95
-38.08
71.32
Superiority
Relative reduction in lesions in SAR442168 15 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model without adjusting for Baseline T2 lesion activity as all participants had at least one T2 lesion at Baseline.
OG000
OG003
SAR442168 30 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.3081
Relative reduction in lesions
38.5
2-Sided
95
-56.61
75.85
Superiority
Relative reduction in lesions in SAR442168 30 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model without adjusting for Baseline T2 lesion activity as all participants had at least one T2 lesion at Baseline.
OG000
OG004
SAR442168 60 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.0001
Relative reduction in lesions
89.34
2-Sided
95
68.39
96.41
Superiority
Relative reduction in lesions in SAR442168 60 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model without adjusting for Baseline T2 lesion activity as all participants had at least one T2 lesion at Baseline.
Cohorts 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG003
Cohorts 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG004
Cohorts 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Units
Counts
Participants
OG00059
OG00131
OG00231
OG00333
OG00431
Title
Denominators
Categories
Title
Measurements
OG0001.36± 3.52
OG0011.77± 4.10
OG0020.87± 1.59
OG0031.18± 4.87
OG0040.29± 0.86
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
SAR442168 5 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.1525
Relative reduction in lesions
-62.16
2-Sided
95
-214.44
16.38
Superiority
Relative reduction in lesions in SAR442168 5 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
OG000
OG002
SAR442168 15 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.4606
Relative reduction in lesions
-47.38
2-Sided
95
-312.91
47.40
Superiority
Relative reduction in lesions in SAR442168 15 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
OG000
OG003
SAR442168 30 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.9490
Relative reduction in lesions
2.90
2-Sided
95
-138.96
60.54
Superiority
Relative reduction in lesions in SAR442168 30 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
OG000
OG004
SAR442168 60 mg/Placebo
Negative binomial regression model
Threshold for significance for p-value was 0.05.
0.2324
Relative reduction in lesions
65.05
2-Sided
95
-96.21
93.77
Superiority
Relative reduction in lesions in SAR442168 60 mg (Cohorts 1 and 2) when compared with placebo (Cohort 2) with 95% CI were reported. Analysis was performed using a negative binomial regression model adjusted for Baseline gadolinium-enhancing T1-hyperintense lesion activity (presence/absence).
Participants who received SAR442168 5 mg orally once daily in Cohort 1.
OG002
Cohort 1: SAR442168 15 mg
Participants who received SAR442168 15 mg orally once daily in Cohort 1.
OG003
Cohort 1: SAR442168 30 mg
Participants who received SAR442168 30 mg orally once daily in Cohort 1.
OG004
Cohort 1: SAR442168 60 mg
Participants who received SAR442168 60 mg orally once daily in Cohort 1.
Units
Counts
Participants
OG00066
OG00116
OG00216
OG00316
OG00416
Title
Denominators
Categories
TEAE
Title
Measurements
OG00023
OG0015
OG0023
OG0032
OG0045
TESAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG002
Cohorts 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG003
Cohorts 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
Units
Counts
Participants
OG00033
OG00132
OG00233
OG00332
Title
Denominators
Categories
TEAE
Title
Measurements
OG00019
OG00117
OG00218
OG00316
TESAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG002
Cohorts 1 and 2: SAR442168 15 mg
All participants who received SAR442168 15 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG003
Cohorts 1 and 2: SAR442168 30 mg
All participants who received SAR442168 30 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.
OG004
Cohorts 1 and 2: SAR442168 60 mg
All participants who received SAR442168 60 mg orally once daily for 12 weeks (either in Cohort 1 or 2) during the 16 weeks treatment period.