Efficacy and Safety Study of Ozanimod in Ulcerative Colitis

Clinical Remission was defined as: Mayo score of \<2 points and with no individual subscore of \> 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. * Stool Frequency Subscore (SFS) * Rectal bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA) Clinical Remission was based on the 4-component Mayo definition.

Time frame: Week 8

Population: The intent to treat ( ITT) population consisted of all randomized participants who received at least one dose of study treatment, with treatment. Participants with missing Mayo scores were classified as non-responders.

The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. * Stool Frequency Subscore (SFS) * Rectal bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA)

Time frame: Baseline to Week 8

Population: The ITT population consisted of all randomized patients who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Includes participants with available data.

A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.

Time frame: From the first dose of IP until 90 days after the last dose of IP or at follow-up visit; the mean total duration of study drug exposure in the OLP was 2.42 years

Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product (IP). All participants in the OLE safety population received 1 mg capsules ozanimod as noted in the description.

A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.

Time frame: From the first dose of investigational product (IP) up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 52.8 days, 56.1 days and 50.8 days respectively for 0.5 mg, 1 mg ozanimod and placebo

Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product (IP).

A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.

Time frame: From the first dose of IP up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 156.3 days, 171.1 days and 154.5 days respectively for 0.5 mg, 1 mg ozanimod and placebo.

Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product (IP) and who entered the maintenance period.

Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Clinical Respone was based on the 4-component Mayo definition.

Time frame: Week 8

Population: The ITT population consisted of all randomized participants who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Participants with missing Mayo score were considered non-responders. Non responder imputation (NRI).

Clinical Remission was defined as: Mayo score of \<2 points and with no individual subscore of \> 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. * Stool Frequency Subscore (SFS) * Rectal bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA)

Time frame: Week 32

Population: The ITT population consisted of all randomized patients who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Participants with missing Mayo score were considered non-responders. Non responder imputation (NRI).

Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. * Stool Frequency Subscore (SFS) * Rectal bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA)

Time frame: Week 32

Population: The ITT population consisted of all randomized patients who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Participants with missing Mayo score were considered non-responders. Non responder imputation (NRI).

Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease 1. = Mild disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 3. = Severe disease (spontaneous bleeding, ulceration)

Time frame: Week 32

Population: The ITT population consisted of all randomized patients who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Non-responder imputation (NRI).

Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease 1. = Mild disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 3. = Severe disease (spontaneous bleeding, ulceration)

Time frame: Week 8

Population: The ITT population consisted of all randomized patients who received at least one dose of study treatment, with treatment assignment designated according to randomized treatment. Non-responder imputation (NRI).