Trial Outcomes & Findings for A Study to Evaluate the Effect of SAR443820 on Serum Neurofilament Levels in Male and Female Adult Participants With Multiple Sclerosis (NCT NCT05630547)

Results Overview

Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal damage. Baseline was defined as the average value of the assessments on screening and Day 1 visits prior to the first dose of the study treatment unless the number of Gadolinium (Gd)-enhancing T1 lesion at Day 1 was greater than zero in which case baseline was the lower value of screening and Day 1 visits.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

Baseline (up to Day 1, pre-dose) and Week 48

Results posted on

2025-10-15

Participant Flow

The study was conducted at 34 centers in 10 countries. A total of 190 participants were screened between 19 December 2022 and 15 September 2023, of which 16 were screen failures. Screen failures were due to not meeting the eligibility criteria.

The study consisted of a screening period (4 weeks before randomization), treatment period (a 48-week double-blind in Part A, an 48-week open-label in Part B, with a maximum total study duration of 100 weeks. A total of 174 participants were randomized and 173 were treated in the study. The study was terminated as it did not meet its primary and key secondary endpoints, therefore Week 96 data was not collected.

Participant milestones

Participant milestones
Measure	Part A: Placebo Participants received placebo matching SAR443820 tablet orally once daily (QD) for 48 weeks in Part A.	Part A: SAR443820 Participants received SAR443820 20 milligram (mg) tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A (Double-blind Period: 48 Weeks) STARTED	86	88	0	0
Part A (Double-blind Period: 48 Weeks) Randomized and Treated	86	87	0	0
Part A (Double-blind Period: 48 Weeks) COMPLETED	77	68	0	0
Part A (Double-blind Period: 48 Weeks) NOT COMPLETED	9	20	0	0
Part B (Open-label Period: 48 Weeks) STARTED	0	0	77	68
Part B (Open-label Period: 48 Weeks) COMPLETED	0	0	0	0
Part B (Open-label Period: 48 Weeks) NOT COMPLETED	0	0	77	68

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Placebo Participants received placebo matching SAR443820 tablet orally once daily (QD) for 48 weeks in Part A.	Part A: SAR443820 Participants received SAR443820 20 milligram (mg) tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A (Double-blind Period: 48 Weeks) Other	0	2	0	0
Part A (Double-blind Period: 48 Weeks) Withdrawal by Subject	8	3	0	0
Part A (Double-blind Period: 48 Weeks) Lack of Efficacy	0	1	0	0
Part A (Double-blind Period: 48 Weeks) Adverse Event	1	13	0	0
Part A (Double-blind Period: 48 Weeks) Randomized and not treated	0	1	0	0
Part B (Open-label Period: 48 Weeks) Study terminated by sponsor	0	0	72	62
Part B (Open-label Period: 48 Weeks) Non-compliance with study schedule	0	0	0	1
Part B (Open-label Period: 48 Weeks) Withdrawal by Subject	0	0	1	3
Part B (Open-label Period: 48 Weeks) Lack of Efficacy	0	0	1	1
Part B (Open-label Period: 48 Weeks) Adverse Event	0	0	3	1

Baseline Characteristics

A Study to Evaluate the Effect of SAR443820 on Serum Neurofilament Levels in Male and Female Adult Participants With Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo n=86 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=88 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Total n=174 Participants Total of all reporting groups
Age, Continuous	47.27 years STANDARD_DEVIATION 9.54 • n=5 Participants	48.22 years STANDARD_DEVIATION 8.21 • n=7 Participants	47.75 years STANDARD_DEVIATION 8.88 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	53 Participants n=7 Participants	107 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	74 Participants n=7 Participants	143 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (up to Day 1, pre-dose) and Week 48

Population: The modified intent-to-treat (mITT) population consisted of all randomized participants who took at least 1 dose of study treatment and with an evaluable primary endpoint. Only participants with data collected at baseline and Week 48 are reported.

Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal damage. Baseline was defined as the average value of the assessments on screening and Day 1 visits prior to the first dose of the study treatment unless the number of Gadolinium (Gd)-enhancing T1 lesion at Day 1 was greater than zero in which case baseline was the lower value of screening and Day 1 visits.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=80 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=85 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Change From Baseline to Week 48 in Serum Neurofilament Light Chain (sNfL) Levels Baseline	9.622 picograms per milliliter (pg/mL) Standard Deviation 5.316	10.319 picograms per milliliter (pg/mL) Standard Deviation 7.402	—	—
Part A: Change From Baseline to Week 48 in Serum Neurofilament Light Chain (sNfL) Levels Week 48	0.958 picograms per milliliter (pg/mL) Standard Deviation 6.983	-0.343 picograms per milliliter (pg/mL) Standard Deviation 7.761	—	—

PRIMARY outcome

Timeframe: Baseline (up to Day 1, pre-dose) and Week 72

Population: The mITT population consisted of all randomized participants who took at least 1 dose of study treatment and with an evaluable primary endpoint. Only participants with data collected at baseline and Week 72 are reported.

Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal damage. Baseline was defined as the average value of the assessments on screening and Day 1 visits prior to the first dose of the study treatment unless the number of Gd-enhancing T1 lesion at Day 1 was greater than zero in which case baseline was the lower value of screening and Day 1 visits.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=80 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=85 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Change From Baseline to Week 72 in Serum Neurofilament Light Chain Levels Baseline	9.622 pg/mL Standard Deviation 5.316	10.319 pg/mL Standard Deviation 7.402	—	—
Part B: Change From Baseline to Week 72 in Serum Neurofilament Light Chain Levels Week 72	-0.320 pg/mL Standard Deviation 3.433	-0.270 pg/mL Standard Deviation 5.247	—	—

SECONDARY outcome

Timeframe: Post-baseline (Baseline: Day 1, pre-dose) and up to Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment.

The adjusted number of new Gd-enhancing T1 hyperintense lesions per scan were derived using negative binomial model.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=86 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=87 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Number of New Gadolinium-Enhancing T1 Hyperintense Lesions as Detected by Magnetic Resonance Imaging (MRI)	0.043 new Gd-enhancing T1 lesions per scan Interval 0.02 to 0.088	0.155 new Gd-enhancing T1 lesions per scan Interval 0.071 to 0.337	—	—

SECONDARY outcome

Timeframe: From Week 48 to approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Here, number of participants analyzed = participants with \>=1 new enlarging T1-hyperintense lesions.

Cumulative number of new Gd-enhancing T1 hyperintense lesions detected by MRI, defined as the sum of the individual number of new Gd-enhancing T1 hyperintense lesions at all scheduled visits calculated for each arm/group as a whole.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=5 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=4 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Number of New Gadolinium-Enhancing T1 Hyperintense Lesions as Detected by MRI	14 new Gd-enhancing T1 lesions	13 new Gd-enhancing T1 lesions	—	—

SECONDARY outcome

Timeframe: Post-baseline (Baseline: Day 1, pre-dose) and up to Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment.

The adjusted number of new, enlarging T2 hyperintense lesions per year were derived using negative binomial model.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=86 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=87 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Number of New, Enlarging T2 Hyperintense Lesions as Detected by MRI	1.285 new and enlarging T2 lesions per year Interval 0.645 to 2.561	2.532 new and enlarging T2 lesions per year Interval 1.183 to 5.422	—	—

SECONDARY outcome

Timeframe: From Week 48 to approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Here, number of participants analyzed = participants with \>=1 new and/or enlarging T2-hyperintense lesions.

Cumulative number of new, enlarging T2 hyperintense lesions detected by MRI, defined as the sum of the individual number of new, enlarging T2 hyperintense lesions at all scheduled visits at all scheduled visits calculated for each arm/group as a whole.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=12 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=9 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Number of New, Enlarging T2 Hyperintense Lesions as Detected by MRI	42 new and enlarging T2 lesions	57 new and enlarging T2 lesions	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at baseline and Week 48 are reported.

Time to onset of 12 weeks CDP was defined as time from randomization to onset of an increase in EDSS score (defined as an increase of \>=1.0 point from baseline EDSS score when baseline score was \<=5.5 or an increase of \>=0.5 points from baseline EDSS score when baseline score was \>5.5) confirmed after a 12 weeks interval. EDSS was a scale for assessing neurologic impairment in participants with MS, based on 7 functional systems (FS) in brain which was used to derive score. The standard EDSS assessments of 7 FS (visual, brain stem, pyramidal, cerebellar, sensory, bowel/bladder, and cerebral functions) scoring was performed by assessment of neurologic symptoms in each FS. Ambulation scoring was done to conclude evaluation. Individual FS scores were then used in conjugation with ambulation score to obtain EDSS score which ranged from 0 (normal) to 10 (death due to MS), with higher scores indicating greater disability. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=6 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=6 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Time to Onset of 12 Weeks Confirmed Disability Progression (CDP) From Baseline as Assessed by the Expanded Disability Status Scale (EDSS) Score	12.29 weeks Interval 11.9 to 24.3	24.14 weeks Interval 11.7 to 36.7	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

Time to onset of 24 weeks CDP was defined as time from randomization to onset of an increase in EDSS score (defined as an increase of \>=1.0 point from baseline EDSS score when baseline score was \<=5.5 or an increase of \>=0.5 points from baseline EDSS score when baseline score was \>5.5) confirmed after a 12 weeks interval. EDSS was a scale for assessing neurologic impairment in participants with MS, based on 7 FS in brain which was used to derive score. The standard EDSS assessments of 7 FS (visual, brain stem, pyramidal, cerebellar, sensory, bowel/bladder, and cerebral functions) scoring was performed by assessment of neurologic symptoms in each FS. Ambulation scoring was done to conclude evaluation. Individual FS scores were then used in conjugation with ambulation score to obtain EDSS score which ranged from 0 (normal) to 10 (death due to MS), with higher scores indicating greater disability. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=5 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=3 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Time to Onset of 24 Weeks Confirmed Disability Progression From Baseline as Assessed by the Expanded Disability Status Scale Score	12.43 weeks Interval 12.1 to 24.3	24.14 weeks Interval 24.1 to 24.4	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at baseline and Week 48 are reported.

The 9-HPT was a brief, standardized, quantitative test of upper extremity function (lower bound: 10 seconds; upper bound: 300 seconds). Two consecutive trials with the dominant hand were immediately followed by 2 consecutive trials with the non-dominant hand. The mean time to test completion served as an assessment of the participant's hand dexterity. A participant was asked to place pegs into holes and remove them with the dominant and non-dominant hand for several repetitions. A higher value of overall 9-HPT was indicative of higher disability. An increase of \>=20% from the baseline score in the 9-HPT was considered meaningful worsening. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=3 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=3 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Time to Onset of Sustained 20% Increase in 9-Hole Peg Test (9-HPT) Confirmed Over at Least 12 Weeks	35.86 weeks Interval 11.9 to 36.1	12.14 weeks Interval 11.1 to 36.1	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The 9-HPT was a brief, standardized, quantitative test of upper extremity function (lower bound: 10 seconds; upper bound: 300 seconds). Two consecutive trials with the dominant hand were immediately followed by 2 consecutive trials with the non-dominant hand. The mean time to test completion served as an assessment of the participant's hand dexterity. A participant was asked to place pegs into holes and remove them with the dominant and non-dominant hand for several repetitions. A higher value of overall 9-HPT was indicative of higher disability. An increase of \>20% from the baseline score in the 9-HPT was considered meaningful worsening. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=1 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Time to Onset of Sustained 20% Increase in 9-Hole Peg Test Confirmed Over at Least 24 Weeks	36.1 weeks Interval 36.1 to 36.1	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at baseline and Week 48 are reported.

The T25-FW test was used to assess a participant's walking ability, time in seconds to walk 25 feet (lower bound: 2.2 seconds; upper bound: 180 seconds). The participant was directed to 1 end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly as safely possible with several repetitions. The mean walk time was used for assessment of the participant's walking ability. An increase of \>20% from the baseline score in the T25-FW test was considered as meaningful worsening. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=16 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=8 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Time to Onset of Sustained 20% Increase in Timed 25-Foot Walk Test (T25-FW) Confirmed Over at Least 12 Weeks	12.29 weeks Interval 11.6 to 35.9	18.00 weeks Interval 11.7 to 36.1	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The T25-FW test was used to assess a participant's walking ability, time in seconds to walk 25 feet (lower bound: 2.2 seconds; upper bound: 180 seconds). The participant was directed to one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly as safely possible with several repetitions. The mean walk time was used for assessment of the participant's walking ability. An increase of \>20% from the baseline score in the T25-FW test was considered as meaningful worsening. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=8 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Time to Onset of Sustained 20% Increase in Timed 25-Foot Walk Test Confirmed Over at Least 24 Weeks	12.14 weeks Interval 11.6 to 24.3	18.00 weeks Interval 11.7 to 48.1	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Week 48 (Part A) and approximately up to Week 72 (Part B)

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

EDSS was a scale for assessing neurologic impairment in participants with MS, based on 7 FS in the brain which was used to derive the EDSS (score). The standard EDSS assessments of 7 FS (visual, brain stem, pyramidal, cerebellar, sensory, bowel/bladder, and cerebral functions) scoring was performed by assessment of neurologic symptoms in each FS. Ambulation scoring was done to conclude the evaluation. Individual FS scores were then used in conjugation with ambulation score to obtain EDSS score which ranged from 0 (normal) to 10 (death due to MS), with higher scores indicating greater disability. A negative change from baseline indicates improvement. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=78 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=76 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 n=3 Participants Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 n=1 Participants Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Parts A and B: Change From Baseline in Expanded Disability Status Scale Score	-0.013 score on a scale Standard Deviation 0.611	-0.023 score on a scale Standard Deviation 0.676	-0.167 score on a scale Standard Deviation 0.722	-1.000 score on a scale Standard Deviation NA Standard deviation (SD) cannot be calculated for a single participant.

SECONDARY outcome

Timeframe: Up to Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with RMS (RRMS plus relapsing SPMS) are reported.

Relapse was defined as the occurrence of acute, new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination attributable to MS. Symptoms were as follows: attributed to MS, last for \>=24 hours, present at normal body temperature, and preceded by \>=30 days of clinical stability (no previous MS relapse). The adjusted ARR was derived using negative binomial model with the total number of relapses per participant occurring in the observation period.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=41 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=42 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Annualized Relapse Rate (ARR) of Relapsing Remitting Multiple Sclerosis (RMS) Population	NA relapses per participant-year NA indicates that the number, lower and upper limit of 95% confidence interval (CI) were not estimable due to insufficient number of participants with events.	NA relapses per participant-year NA indicates that the number, lower and upper limit of 95% CI were not estimable due to insufficient number of participants with events.	—	—

SECONDARY outcome

Timeframe: Approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with RMS (RRMS plus relapsing SPMS) are reported.

Relapse was defined as the occurrence of acute, new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination attributable to MS. Symptoms were as follows: attributed to MS, last for \>=24 hours, present at normal body temperature, and preceded by \>=30 days of clinical stability (no previous MS relapse). The unadjusted ARR was the total number of relapses that occurred during the observation period divided by the total participant years in the study.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=41 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=42 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Annualized Relapse Rate of Relapsing Remitting Multiple Sclerosis Population	0.052 relapses per participant-year	0.172 relapses per participant-year	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Week 48 (Part A) and approximately up to Week 72 (Part B)

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate BVL. Imaging measure to detect degree of atrophy or decrease in whole brain, cortical and/or thalamic volume, which was diagnostic evidence of disease progression and played a key role in long-term disability. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=72 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=71 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 n=5 Participants Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 n=4 Participants Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Parts A and B: Percent Change From Baseline in Brain Volume Loss (BVL) as Detected by Brain Magnetic Resonance Imaging	-0.177 percent change Standard Deviation 0.426	-0.397 percent change Standard Deviation 0.462	-0.502 percent change Standard Deviation 0.526	-0.462 percent change Standard Deviation 0.869

SECONDARY outcome

Timeframe: Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate volume of SELs. SELs represent chronic active lesions in MS where there is ongoing, smoldering inflammation primarily driven by activated microglia and macrophages at the lesion edges. This localized, radial expansion causes gradual enlargement of pre-existing T2 MRI lesions over time and leads to progressive neural tissue damage including demyelination, axonal loss, and irreversible central nervous system (CNS) injury.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=71 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=71 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Volume of Slowly Expanding Lesions (SELs)	5.436 microliter (µL) Interval 4.773 to 6.099	5.672 microliter (µL) Interval 4.958 to 6.386	—	—

SECONDARY outcome

Timeframe: Approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate volume of SELs. SELs represent chronic active lesions in MS where there is ongoing, smoldering inflammation primarily driven by activated microglia and macrophages at the lesion edges. This localized, radial expansion causes gradual enlargement of pre-existing T2 MRI lesions over time and leads to progressive neural tissue damage including demyelination, axonal loss, and irreversible CNS injury.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=5 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=4 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Volume of Slowly Expanding Lesions	1485.00 µL Standard Deviation 2657.22	1152.00 µL Standard Deviation 998.67	—	—

SECONDARY outcome

Timeframe: Week 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the intervention allocated by randomization. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate number of SELs. SELs represent chronic active lesions in MS where there is ongoing, smoldering inflammation primarily driven by activated microglia and macrophages at the lesion edges. This localized, radial expansion causes gradual enlargement of pre-existing T2 MRI lesions over time and leads to progressive neural tissue damage including demyelination, axonal loss, and irreversible CNS injury.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=71 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=71 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Number of Slowly Expanding Lesions	1.507 number of SEL Interval 1.296 to 1.718	1.534 number of SEL Interval 1.307 to 1.761	—	—

SECONDARY outcome

Timeframe: Approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate number of SELs. SELs represent chronic active lesions in MS where there is ongoing, smoldering inflammation primarily driven by activated microglia and macrophages at the lesion edges. This localized, radial expansion causes gradual enlargement of pre-existing T2 MRI lesions over time and leads to progressive neural tissue damage including demyelination, axonal loss, and irreversible CNS injury.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=5 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=4 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Number of Slowly Expanding Lesions	6.60 number of SEL Standard Deviation 9.84	6.25 number of SEL Standard Deviation 5.32	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose), Weeks 12, 24, 36, and 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate normalization of T1 intensity of SELs. It was used to quantify tissue damage within SELs of MS, reflecting neuro-axonal loss and demyelination and correlating with clinical progression.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=61 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=71 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Normalized T1 Intensity of Slowly Expanding Lesions Baseline (Day 1, pre-dose)	-0.055 ratio Standard Deviation 0.346	0.008 ratio Standard Deviation 0.354	—	—
Part A: Normalized T1 Intensity of Slowly Expanding Lesions Week 12	-0.066 ratio Standard Deviation 0.369	-0.026 ratio Standard Deviation 0.325	—	—
Part A: Normalized T1 Intensity of Slowly Expanding Lesions Week 24	-0.096 ratio Standard Deviation 0.352	-0.031 ratio Standard Deviation 0.341	—	—
Part A: Normalized T1 Intensity of Slowly Expanding Lesions Week 36	-0.107 ratio Standard Deviation 0.355	-0.053 ratio Standard Deviation 0.350	—	—
Part A: Normalized T1 Intensity of Slowly Expanding Lesions Week 48	-0.123 ratio Standard Deviation 0.357	-0.058 ratio Standard Deviation 0.370	—	—

SECONDARY outcome

Timeframe: Week 48 and Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan was performed at all sites and used to evaluate normalized T1 intensity of SELs. It was used to quantify tissue damage within SELs of MS, reflecting neuro-axonal loss and demyelination and correlating with clinical progression.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=3 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=3 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Normalized T1 Intensity of Slowly Expanding Lesions Week 48	-0.342 ratio Standard Deviation 0.118	-0.083 ratio Standard Deviation 0.241	—	—
Part B: Normalized T1 Intensity of Slowly Expanding Lesions Week 72	-0.507 ratio Standard Deviation 0.236	-0.183 ratio Standard Deviation 0.201	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Weeks 12, 24, 36, and 48

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan sequences were performed at all sites and used to evaluate number of PRL. Phase rim lesions were a subtype of MS lesion identified by a paramagnetic edge indicative chronic smoldering inflammation linked to chronic active lesions. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=40 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=38 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Change From Baseline in the Number of Phase Rim Lesions (PRL) Conducted at 3 Tesla (3T) Capable Sites Week 12	0.05 phase rim lesions Standard Deviation 0.22	0.00 phase rim lesions Standard Deviation 0.00	—	—
Part A: Change From Baseline in the Number of Phase Rim Lesions (PRL) Conducted at 3 Tesla (3T) Capable Sites Week 24	0.11 phase rim lesions Standard Deviation 0.65	0.00 phase rim lesions Standard Deviation 0.00	—	—
Part A: Change From Baseline in the Number of Phase Rim Lesions (PRL) Conducted at 3 Tesla (3T) Capable Sites Week 36	0.11 phase rim lesions Standard Deviation 0.83	0.00 phase rim lesions Standard Deviation 0.00	—	—
Part A: Change From Baseline in the Number of Phase Rim Lesions (PRL) Conducted at 3 Tesla (3T) Capable Sites Week 48	0.14 phase rim lesions Standard Deviation 1.02	-0.03 phase rim lesions Standard Deviation 0.18	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The basic MRI scan sequences were performed at all sites and used to evaluate number of PRL. Phase rim lesions were a subtype of MS lesion identified by a paramagnetic edge indicative chronic smoldering inflammation linked to chronic active lesions. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=3 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=4 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Change From Baseline in the Number of Phase Rim Lesions Conducted at 3 Tesla Capable Sites	2.33 phase rim lesions Standard Deviation 4.93	-0.25 phase rim lesions Standard Deviation 0.50	—	—

SECONDARY outcome

Timeframe: From first dose of SAR443820 (Day 1, post-dose) up to 14 days after last dose of SAR443820 administration in Part B, approximately 93 weeks for Parts A+B combined arm (SAR443820/SAR443820), approximately 45 weeks Part B Arm (Placebo/SAR443820)

Population: Safety population consisted of all randomized participants who took at least 1 dose of SAR443820. All participants from safety population and treated with SAR443820 are included in Part B arm and participants from safety population are included in Parts A+B arm. The combined safety analysis for TEAE provided the accurate summary of all TEAE in both treatment groups after the initiation of SAR443820.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from first administration of study treatment (Day 1) to last administration of study treatment + 14 days). SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. All TEAE occurring after SAR443820 initiation are provided for both randomized treatment arms in this endpoint.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=77 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=164 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Parts B and A+B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) After SAR443820 Initiation TEAEs	39 Participants	108 Participants	—	—
Parts B and A+B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) After SAR443820 Initiation TESAEs	5 Participants	7 Participants	—	—

SECONDARY outcome

Timeframe: Day 1: 0.25-1 hour and 1-3 hours post-dose; Week 2: pre-dose, 0.5-3 hours post-dose; Weeks 6, 12, and 36: pre-dose

Population: Pharmacokinetic (PK) population consisted of all randomized and treated participants with at least 1 post-baseline PK result with adequate documentation of dosing and sampling dates and times. Only participants who received SAR443820 with data collected at specified timepoints are reported.

Plasma samples were collected at specified timepoints to determine plasma concentrations of SAR443820.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=540 Samples Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part A: Plasma Concentration of SAR443820 Week 36: pre-dose	56.461 nanogram/mL Standard Deviation 60.180	—	—	—
Part A: Plasma Concentration of SAR443820 Day 1: 0.25-1 hours post-dose	205.450 nanogram/mL Standard Deviation 134.734	—	—	—
Part A: Plasma Concentration of SAR443820 Day 1: 1-3 hours post-dose	237.232 nanogram/mL Standard Deviation 92.001	—	—	—
Part A: Plasma Concentration of SAR443820 Week 2: pre-dose	52.841 nanogram/mL Standard Deviation 54.432	—	—	—
Part A: Plasma Concentration of SAR443820 Week 2: 0.5-3 hours post-dose	289.312 nanogram/mL Standard Deviation 129.688	—	—	—
Part A: Plasma Concentration of SAR443820 Week 6: pre-dose	45.230 nanogram/mL Standard Deviation 41.458	—	—	—
Part A: Plasma Concentration of SAR443820 Week 12: pre-dose	49.039 nanogram/mL Standard Deviation 41.203	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

Time to onset of 24-week CCDP, was assessed by composite endpoint EDSS-Plus (EDSS score, or T25-FW test, or 9-HPT), was confirmed over at least 24 week. The EDSS-plus event was defined as disability progression on at least 1 of 3 components, EDSS score, or T25-FW test, or 9-HPT. Disability criteria for the individual components are defined as follows: Disability progression on the EDSS was defined as an increase of \>=1.0 point from the baseline EDSS score when the baseline score was \<=5.5 or an increase of \>=0.5 points from the baseline EDSS score when the baseline score was \>5.5. Disability progression on the T25-FW test was defined as an increase (worsening) of \>=20% from the baseline score. Disability progression on the 9-HPT was defined as an increase (worsening) of \>=20% from the baseline score. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=12 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=10 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Time to Onset of Composite Confirmed Disability Progression Confirmed Over at Least 24 Weeks	12.29 weeks Interval 11.6 to 36.1	24.00 weeks Interval 11.7 to 48.1	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The MSIS-29v2 evaluates the specific physical and psychological impact of MS from a participant's perspective. This participant reported outcome instrument has 2 subscales: a physical impact score (20 items) and a psychological impact score (9 items). The physical and psychological impact subscales of the MSIS-29v2 range from 0 to 100, with higher scores indicating greater physical or psychological impact. Each of the 2 scales are scored by summing the responses across items, then converting to score range 0-100 where 100 indicates greater impact of disease on daily function (worse health). Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=3 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Change From Baseline in Multiple Sclerosis Impact Scale-29 Version 2 (MSIS-29v2) Physical and Psychological Domains Scores Physical domains score	11.667 score on a scale Standard Deviation 28.447	2.222 score on a scale Standard Deviation 1.925	—	—
Part B: Change From Baseline in Multiple Sclerosis Impact Scale-29 Version 2 (MSIS-29v2) Physical and Psychological Domains Scores Psychological domains score	13.889 score on a scale Standard Deviation 52.498	4.938 score on a scale Standard Deviation 5.658	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose) and approximately up to Week 72

Population: Randomized and treated population consisted of all randomized participants who took at least 1 dose of study treatment. Only participants with data collected at specified timepoints are reported.

The MSWS-12 measured the impact of walking impairment in participants with MS. This participant reported outcome instrument has 12 items with a global score ranging from 0 to 100. A higher score indicates better quality of life. The MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100, with higher score indicating better quality of life. Baseline was defined as Day 1 (pre-dose).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=3 Participants Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=3 Participants Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Part B: Change From Baseline in Multiple Sclerosis Walking Scale 12 Items (MSWS-12) Scores	4.861 score on a scale Standard Deviation 17.472	-1.389 score on a scale Standard Deviation 6.365	—	—

Adverse Events

Part A: Placebo

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Part A: SAR443820

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Part B: Placebo/SAR443820

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Part B: SAR443820/SAR443820

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Placebo n=86 participants at risk Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=87 participants at risk Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 n=77 participants at risk Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 n=68 participants at risk Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Infections and infestations Erysipelas	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.1% 1/87 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Nervous system disorders Multiple Sclerosis Relapse	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Vascular disorders Deep Vein Thrombosis	1.2% 1/86 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Hepatobiliary disorders Hepatitis Toxic	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.1% 1/87 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Hepatobiliary disorders Liver Injury	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Concussion	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.1% 1/87 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Head Injury	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Lower Limb Fracture	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Tendon Rupture	0.00% 0/86 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/87 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.

Other adverse events

Other adverse events
Measure	Part A: Placebo n=86 participants at risk Participants received placebo matching SAR443820 tablet orally QD for 48 weeks in Part A.	Part A: SAR443820 n=87 participants at risk Participants received SAR443820 20 mg tablet orally QD for 48 weeks in Part A.	Part B: Placebo/SAR443820 n=77 participants at risk Participants who had received placebo matching SAR443820 tablet in Part A, received SAR443820 20 mg tablet orally QD for 48 weeks during Part B.	Part B: SAR443820/SAR443820 n=68 participants at risk Participants who had received SAR443820 tablet in Part A, continued to receive SAR443820 20 mg tablet orally QD for 48 weeks during Part B.
Infections and infestations Covid-19	7.0% 6/86 • Number of events 6 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	9.2% 8/87 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	5.2% 4/77 • Number of events 4 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	8.1% 7/86 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	4.6% 4/87 • Number of events 4 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	2.9% 2/68 • Number of events 2 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	5.8% 5/86 • Number of events 5 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	4.6% 4/87 • Number of events 4 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.5% 1/68 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Infections and infestations Urinary Tract Infection	4.7% 4/86 • Number of events 5 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	8.0% 7/87 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	2.9% 2/68 • Number of events 2 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Nervous system disorders Headache	7.0% 6/86 • Number of events 7 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	5.7% 5/87 • Number of events 7 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	3.9% 3/77 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Investigations Alanine Aminotransferase Increased	1.2% 1/86 • Number of events 2 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	8.0% 7/87 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	3.9% 3/77 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	2.9% 2/68 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Investigations Aspartate Aminotransferase Increased	1.2% 1/86 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	6.9% 6/87 • Number of events 6 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	2.9% 2/68 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Investigations Hepatic Enzyme Increased	1.2% 1/86 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	17.2% 15/87 • Number of events 15 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	3.9% 3/77 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Accidental Overdose	10.5% 9/86 • Number of events 15 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	6.9% 6/87 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	1.3% 1/77 • Number of events 1 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/68 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Fall	8.1% 7/86 • Number of events 8 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	3.4% 3/87 • Number of events 4 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	0.00% 0/77 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.	4.4% 3/68 • Number of events 3 • Adverse events were collected from first dose of study treatment (Day 1, post-dose) up to 14 days after last dose of study treatment administration, up to 50 weeks for Part A, and 45 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form (Week -4) to study termination, approximately 100 weeks. Analysis was performed on safety population.

Additional Information

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