Relapsing Multiple Sclerosis
Conditions
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.
Interventions
DRUGSAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral
DRUGPlacebo
Pharmaceutical form: Film coated tablet; Route of administration: Oral
DRUGLocally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of New or Enlarging T2 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 | 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). |
| Total Number of Gd-enhancing T1-hyperintense 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 | 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). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | From Baseline up to Week 4 | 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. |
| Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants | 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). |
| Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | 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 | 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. |
Countries
Canada, Czechia, Estonia, France, Netherlands, Russia, Slovakia, Spain, Ukraine, United States
Participant flow
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.
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 \[all considered as Cohort 2\]).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| 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. | 16 |
| 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. | 16 |
| 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. | 16 |
| 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. | 17 |
| 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. | 16 |
| 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. | 17 |
| 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. | 16 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: SAR442168 5 mg Then Placebo | Total | Cohort 2: Placebo Then SAR442168 60 mg | Cohort 2: Placebo Then SAR442168 30 mg | Cohort 2: Placebo Then SAR442168 15 mg | Cohort 2: Placebo Then SAR442168 5 mg | Cohort 1: SAR442168 60 mg Then Placebo | Cohort 1: SAR442168 30 mg Then Placebo | Cohort 1: SAR442168 15 mg Then Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 11.1 | 37.1 years STANDARD_DEVIATION 9.5 | 36.1 years STANDARD_DEVIATION 8.7 | 37.5 years STANDARD_DEVIATION 11.6 | 36.7 years STANDARD_DEVIATION 10.7 | 34.8 years STANDARD_DEVIATION 8.6 | 38.1 years STANDARD_DEVIATION 9.1 | 40.8 years STANDARD_DEVIATION 8.7 | 35.1 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 15 Participants | 119 Participants | 14 Participants | 16 Participants | 14 Participants | 17 Participants | 15 Participants | 13 Participants | 15 Participants |
| Sex: Female, Male Female | 9 Participants | 91 Participants | 9 Participants | 10 Participants | 11 Participants | 16 Participants | 15 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 39 Participants | 7 Participants | 7 Participants | 5 Participants | 1 Participants | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 32 | 0 / 33 | 0 / 32 | 0 / 64 | 0 / 66 |
| other Total, other adverse events | 19 / 33 | 17 / 32 | 18 / 33 | 16 / 32 | 10 / 64 | 23 / 66 |
| serious Total, serious adverse events | 0 / 33 | 0 / 32 | 0 / 33 | 1 / 32 | 0 / 64 | 0 / 66 |
Outcome results
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions | 1.03 lesions | Standard Deviation 2.5 |
| Cohorts 1 and 2: SAR442168 5 mg | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions | 1.39 lesions | Standard Deviation 3.2 |
| Cohorts 1 and 2: SAR442168 15 mg | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions | 0.77 lesions | Standard Deviation 1.48 |
| Cohorts 1 and 2: SAR442168 30 mg | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions | 0.76 lesions | Standard Deviation 3.31 |
| Cohorts 1 and 2: SAR442168 60 mg | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions | 0.13 lesions | Standard Deviation 0.43 |
Comparison: SAR442168 5 mg/Placebop-value: 0.167395% CI: [-193.99, 17.05]Negative binomial regression model
Comparison: SAR442168 15 mg/Placebop-value: 0.35495% CI: [-356.24, 41.91]Negative binomial regression model
Comparison: SAR442168 30 mg/Placebop-value: 0.767495% CI: [-126.05, 66.89]Negative binomial regression model
Comparison: SAR442168 60 mg/Placebop-value: 0.017895% CI: [28.02, 96.88]Negative binomial regression model
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Number of New or Enlarging T2 Lesions | 2.12 lesions | Standard Deviation 5.16 |
| Cohorts 1 and 2: SAR442168 5 mg | Number of New or Enlarging T2 Lesions | 1.90 lesions | Standard Deviation 3.97 |
| Cohorts 1 and 2: SAR442168 15 mg | Number of New or Enlarging T2 Lesions | 1.32 lesions | Standard Deviation 1.83 |
| Cohorts 1 and 2: SAR442168 30 mg | Number of New or Enlarging T2 Lesions | 1.30 lesions | Standard Deviation 4.9 |
| Cohorts 1 and 2: SAR442168 60 mg | Number of New or Enlarging T2 Lesions | 0.23 lesions | Standard Deviation 0.62 |
Comparison: SAR442168 5 mg/Placebop-value: 0.773695% CI: [-86.49, 56.73]Negative binomial regression model
Comparison: SAR442168 15 mg/Placebop-value: 0.24895% CI: [-38.08, 71.32]Negative binomial regression model
Comparison: SAR442168 30 mg/Placebop-value: 0.308195% CI: [-56.61, 75.85]Negative binomial regression model
Comparison: SAR442168 60 mg/Placebop-value: 0.000195% CI: [68.39, 96.41]Negative binomial regression model
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.
Time frame: 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
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Vitals | 0 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Hematology | 0 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | ECGs | 0 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Chemistry | 0 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Urinalysis | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Vitals | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Urinalysis | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Chemistry | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | ECGs | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Hematology | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Urinalysis | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Hematology | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Chemistry | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Vitals | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | ECGs | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | ECGs | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Hematology | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Vitals | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Urinalysis | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Chemistry | 0 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Urinalysis | 0 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Vitals | 0 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Hematology | 0 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | ECGs | 0 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) | Chemistry | 0 Participants |
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).
Time frame: Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TEAE | 19 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TEAE | 17 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TEAE | 18 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TEAE | 16 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period | TESAE | 1 Participants |
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.
Time frame: From Baseline up to Week 4
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TEAE | 23 Participants |
| Cohort 2: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TEAE | 5 Participants |
| Cohorts 1 and 2: SAR442168 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TEAE | 3 Participants |
| Cohorts 1 and 2: SAR442168 15 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TESAE | 0 Participants |
| Cohorts 1 and 2: SAR442168 30 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TEAE | 2 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TEAE | 5 Participants |
| Cohorts 1 and 2: SAR442168 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period | TESAE | 0 Participants |
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Pooled Placebo | Total Number of Gd-enhancing T1-hyperintense Lesions | 1.36 lesions | Standard Deviation 3.52 |
| Cohorts 1 and 2: SAR442168 5 mg | Total Number of Gd-enhancing T1-hyperintense Lesions | 1.77 lesions | Standard Deviation 4.1 |
| Cohorts 1 and 2: SAR442168 15 mg | Total Number of Gd-enhancing T1-hyperintense Lesions | 0.87 lesions | Standard Deviation 1.59 |
| Cohorts 1 and 2: SAR442168 30 mg | Total Number of Gd-enhancing T1-hyperintense Lesions | 1.18 lesions | Standard Deviation 4.87 |
| Cohorts 1 and 2: SAR442168 60 mg | Total Number of Gd-enhancing T1-hyperintense Lesions | 0.29 lesions | Standard Deviation 0.86 |
Comparison: SAR442168 5 mg/Placebop-value: 0.152595% CI: [-214.44, 16.38]Negative binomial regression model
Comparison: SAR442168 15 mg/Placebop-value: 0.460695% CI: [-312.91, 47.4]Negative binomial regression model
Comparison: SAR442168 30 mg/Placebop-value: 0.94995% CI: [-138.96, 60.54]Negative binomial regression model
Comparison: SAR442168 60 mg/Placebop-value: 0.232495% CI: [-96.21, 93.77]Negative binomial regression model