An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was 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 disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the respective on-treatment periods.

The safety population included all participants enrolled in this study and exposed to study drug, regardless of the amount of exposure.

Magnetic resonance imaging (MRI) of the brain was performed to identify number of new Gd-enhancing T1-hyperintense lesions. Central review was used to identify new Gd-enhancing T1-hyperintense lesions not present at the previous MRI. mITT=modified intent-to-treat; SAP= statistical analysis plan. Only those participants with data collected at specified timepoints are reported.

The mITT population included all participants enrolled in this study who had at least 1 day of study drug exposure during study. As pre-specified in protocol and SAP, the main objective of this study was to determine the long-term efficacy of selected Phase 3 dose (60 mg). Part A was a short transition period while picking phase 3 dose; no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60 and 60/60 mg.

MRI of the brain was performed to identify number of new or enlarging T2 lesions. Central review was used to identify new or enlarging T2 lesions not present at the previous MRI; the values were standardized to per month values by dividing by the number of months (4-week intervals) from the previous MRI to the current MRI.

Analysis was performed on the mITT population. As pre-specified in protocol and SAP,main objective of this study was to determine long-term efficacy of selected Phase 3 dose (60 mg).Part A was a short transition period while picking phase 3 dose;no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60, and 60/60 mg. Only those participants with data collected at specified timepoints are reported.

MRI of the brain was performed to identify number of Gd-enhancing T1-hyperintense lesions. Central review was used to identify Gd-enhancing T1-hyperintense lesions not present at the previous MRI.

Analysis was performed on the mITT population. As pre-specified in protocol and SAP,main objective of this study was to determine long-term efficacy of selected Phase 3 dose (60 mg).Part A was a short transition period while picking phase 3 dose;no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60, and 60/60 mg. Only those participants with data collected at specified timepoints are reported.

Multiple sclerosis (MS) relapse was defined as acute, new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for >=24 hours with or without recovery, present at normal body temperature and preceded by >=30 days of clinical stability. ARR was the total number of relapses for participants by dose group divided by the sum of the standardized study duration for participants in the dose group.

Analysis was performed on the mITT population. As pre-specified in protocol and SAP,main objective of this study was to determine long-term efficacy of selected Phase 3 dose (60 mg).Part A was a short transition period while picking phase 3 dose;no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60, and 60/60 mg.

The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal (motor), cerebellar (coordination), sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Baseline assessed for long-term tolebrutinib treatment by change from baseline was defined as the last non-missing value prior to the first administration of randomized study drug in DRI15928 study.

Analysis was performed on the mITT population. As pre-specified in protocol and SAP,main objective of this study was to determine long-term efficacy of selected Phase 3 dose (60 mg).Part A was a short transition period while picking phase 3 dose;no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60, and 60/60 mg. Only those participants with data collected at specified timepoints are reported.