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

Study Overview
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Brief Summary
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This study is a two-part trial consisting of Part A (presented in this record) and Part B (see NCT02047734). The primary objective in Part A of this study was to demonstrate the superior efficacy of ozanimod compared to placebo by showing a reduction in the cumulative number of total gadolinium-enhancing (GdE) lesions from Week 12 to Week 24 in patients with relapsing multiple sclerosis (RMS).

Official Title
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A Phase 2/3, Multi-center, Randomized, Double-blind, Placebo-controlled (Part A) and Double-blind, Double-dummy, Active-controlled (Part B), Parallel Group Study to Evaluate the Efficacy and Safety of RPC1063 Administered Orally to Relapsing Multiple Sclerosis Patients

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: Ozanimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multiple sclerosis as diagnosed by the revised 2010 McDonald criteria Expanded Disability Status Scale (EDSS) score between 0 and 5.0 at Baseline Exclusion Criteria: Secondary or primary progressive multiple sclerosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ozanimod 0.5 mg<br>Participants received ozanimod 0.5 mg oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and continue to receive ozanimod 0.5 mg weekly for another 96 weeks. | Drug: Ozanimod<br>* Oral capsule taken once a day<br>* Other names: Zeposia®;|
| Experimental: Ozanimod 1 mg<br>Participants received ozanimod 0.5 mg oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and continue to receive ozanimod 1 mg weekly for another 96 weeks. | Drug: Ozanimod<br>* Oral capsule taken once a day<br>* Other names: Zeposia®;|
| Placebo Comparator: Placebo<br>Participants received placebo to ozanimod oral capsules daily for 24 weeks. Participants who completed the 24-week treatment period had the option to enter the blinded extension period and were randomized to receive ozanimod 0.5 mg or 1 mg weekly for 96 weeks. | Drug: Ozanimod<br>* Oral capsule taken once a day<br>* Other names: Zeposia®;Drug: Placebo<br>* Oral capsule taken once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Gadolinium-Enhancing (GdE) Lesions Assessed on Brain Magnetic Resonance Imaging (MRI) From Week 12 to Week 24 | 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. | From Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Gadolinium-Enhancing Lesions on Brain MRI Scan at Week 24 | MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes. | Week 24 | 
| The Total Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions From Week 12 to Week 24 | 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. | Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24 | 
| Adjusted Annualized Relapse Rate (ARR) at Week 24 | 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. | Week 24 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Treatment Period | 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. | 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. | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE) During Ozanimod Exposure | 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. | 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. |