Efficacy and Safety Study of Ozanimod (RPC1063) in Relapsing Multiple Sclerosis Patients

The cumulative number of total GdE lesions on MRI from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time frame: From Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24

Population: The ITT population is defined as all randomized participants who received at least 1 dose of study drug.~Missing data were imputed using the last valid non-missing, post-baseline observation which was carried forward if the participant was only missing 1 or 2 consecutive post-baseline scans. If there were no post-baseline data or the participant was missing \> 2 consecutive scans, the mean number of lesions from participants in the same treatment group and visit was used as the imputed value.

A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for \> 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores. Relapse rate was calculated as the total number of confirmed relapses divided by the total number of days in the study \* 365. ARR was based on a Poisson regression model, adjusted for region, relapses within 24 months before the study, and presence of gadolinium-enhancing lesions at Baseline.

Time frame: Week 24

Population: The ITT population is defined as all randomized participants who received at least 1 dose of study drug.

AEs are reported from the start of the placebo-controlled period for participants originally assigned to ozanimod and from the start of the extension period for participants who switched to ozanimod after Week 24. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes. The investigator assessed the severity of AEs as mild, moderate, or severe, and the relationship of each AE to treatment based on timing and other known factors such as clinical state, environment, or other therapies.

Time frame: From the first dose of ozanimod, either in the placebo-controlled or the blinded extension period, up to 4 weeks after the last dose; mean duration of exposure was 25.4, 30.9, 24.6, and 32.3 months in each treatment group respectively.

Population: Safety population was defined as all participants who received at least one dose of study drug in the blinded extension phase

An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP), including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes. The investigator assessed the severity of AEs as mild, moderate, or severe, and the relationship of each AE to treatment as unrelated, unlikely, possible, probable, or related based on timing and other known factors such as clinical state, environment, or other therapies.

Time frame: From first dose of study drug up to Week 24, or up to 28 days after the last dose for participants who did not enter the extension period.

Population: Safety population was defined as all participants who received at least one dose of study drug.

MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time frame: Week 24

Population: The ITT population is defined as all randomized participants who received at least 1 dose of study drug. Missing GdE data values were imputed using the mean number of lesions from participants in the same treatment group at the same visit.

The cumulative number of new or enlarging hyperintense T2-weighted brain MRI lesions from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time frame: Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24

Population: The ITT population is defined as all randomized participants who received at least 1 dose of study drug. Missing new or enlarging T2 data values were imputed using the mean from participants of the same treatment group at the same visit.

MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time frame: Weeks 24, 48, 72, and 120

Population: Participants who entered the blinded extension period, received at least 1 dose of study drug, and had any post-baseline assessment in the blinded extension period. Includes participants with non-missing MRI results at each time point.

The cumulative number of new or enlarging hyperintense T2-weighted brain MRI lesions from Week 12 to Week 24 in the placebo controlled period (reference) and during the first and second years of the extension period. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time frame: Weeks 12 to 24 of the placebo-controlled period and Week 24 to 72 (first year) and Week 72 - 120 (second year) in the extension period

Population: Participants who entered the blinded extension period, received at least 1 dose of study drug, and had any post-baseline assessment in the blinded extension period. Includes participants with non-missing MRI results in each time period.