Study of Ozanimod (RPC1063) in Relapsing Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ozanimod is effective in the treatment of relapsing multiple sclerosis (RMS).

Official Title
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A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy, Active Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of RPC1063 Administered Orally To Relapsing Multiple Sclerosis Patients

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Ozanimod
* Drug: Interferon beta-1a
* Drug: Placebo to ozanimod
* Drug: Placebo to interferon beta-1a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multiple sclerosis as diagnosed by the revised 2010 McDonald criteria EDSS score between 0 and 5.0 at baseline Exclusion Criteria: • 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 |
| --- | --- |
| Active Comparator: Interferon beta-1a<br>Participants received 30 µg interferon beta-1a by intramuscular (IM) injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally once a day until the last participant had been treated for 12 months. | Drug: Interferon beta-1a<br>* Administered by intramuscular injection once a week<br>* Other names: IFN β-1a;Drug: Placebo to ozanimod<br>* Matching placebo capsules administered orally once a day<br>|
| Experimental: Ozanimod 0.5 mg<br>Participants received ozanimod 0.5 mg capsules orally once a day and an intramuscular placebo injection (identical in appearance to Interferon) weekly until the last participant had been treated for 12 months. | Drug: Ozanimod<br>* Capsules for oral administration once a day<br>* Other names: Zeposia®;Drug: Placebo to interferon beta-1a<br>* Placebo intramuscular injection once a week<br>|
| Experimental: Ozanimod 1 mg<br>Participants received ozanimod 1 mg capsules orally once a day and an intramuscular placebo injection (identical in appearance to Interferon) weekly until the last participant had been treated for 12 months. | Drug: Ozanimod<br>* Capsules for oral administration once a day<br>* Other names: Zeposia®;Drug: Placebo to interferon beta-1a<br>* Placebo intramuscular injection once a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Annualized Relapse Rate (ARR) During the Treatment Period | The relapse rate was based on confirmed relapses. 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 relapses divided by the total number of days in the study * 365.25. ARR was adjusted for region (Eastern Europe vs rest of world), Baseline age, and Baseline number of gadolinium-enhancing lesions; the natural log transformation of time on study was included as an offset term. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months | The number of new or enlarging hyperintense T2-weighted brain MRI lesions per scan was based on the cumulative number of new or enlarging T2 lesions since Baseline over treatment period. | 12 month treatment period; MRI scans were assessed at Month 6 and Month 12 | 
| Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12 |  | Month 12 | 
| Time to Onset of Disability Progression Confirmed After 3 Months | EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present. The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments. Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 3 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later. | From first dose to the end of the 12-month treatment period | 
| Time to Onset of Disability Progression Confirmed After 6 Months | EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present. The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments. Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 6 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later. | From first dose to the end of the 12-month treatment period | 
| Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12 | MRI scans were analyzed by blinded centralized reading facility. | Month 12 | 
| Percentage of Participants Who Were T2 Lesion-Free at Month 12 | MRI scans were analyzed by blinded centralized reading facility. | Month 12 | 
| Percent Change From Baseline in Normalized Brain Volume at Month 12 | Brain volume (a measure of brain atrophy) was analyzed by MRI. | Baseline to Month 12 | 
| Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test | The MSFC-LCLA is a battery including the following 4 individual scales: Timed 25-Foot Walk is an ambulation measure of walking 25 feet with time taken recorded in seconds 9-Hole Peg Test (9HPT) is a quantitative measure of upper extremity (arm and hand) function Symbol Digit Modalities Test (SDMT) is a measure of executive cognitive function that assesses processing speed, flexibility, and calculation ability Low-Contrast Letter Acuity Test (LCLA) used a standardized set of charts to assess low contrast visual acuity, charts are scored according to the number of letters that are identified correctly Z-scores were calculated for for each component and averaged to create an overall composite score, using the study population as the reference population. A z-score represents the number of standard deviations a patient's test result is higher (z > 0) or lower (z < 0) than the average test result (z = 0) of the reference population. A positive change indicates improvement. | Baseline to Month 12 | 
| Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores | The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. The instrument includes 12 subscales, two summary scores, and two single-item measures. The two summary scores - physical health and mental health - are derived from a weighted combination of scale scores. The physical health composite score includes Physical function, Health perceptions, Energy/fatigue, Role limitations - physical, Pain, Sexual function, Social function, and Health distress. The mental health composite score includes Health distress, Overall quality of life, Emotional well-being, Role limitations - emotional, and Cognitive function. Each composite summary score has a range from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement. | Baseline to Month 12 | 
| Number of Participants With Treatment Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP). An AE can be any unfavorable or unintended sign, including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. A serious AE (SAE) is any untoward medical occurrence or effect that results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization. The investigator assessed the severity of AEs as mild, moderate, or severe. | From the first dose of study drug until 28 days following the last dose of study drug; mean exposure to study drug was 13.5 months for interferon beta-1a and 13.6 months for each ozanimod group. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, RMS, Multiple Sclerosis, Relapsing Multiple Sclerosis