Study Describing Cognitive Processing Speed Changes in Relapsing Multiple Sclerosis Subjects Treated With Ozanimod (RPC-1063)

Study Overview
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Brief Summary
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This is a multicenter, longitudinal, single-arm, open-label study to describe the change from baseline in cognitive processing speed, measured by the SDMT, in subjects with RMS treated with ozanimod HCl 1 mg at 3 years. All subjects will receive orally administered ozanimod HCl 1 mg. The primary efficacy endpoint is the proportion of subjects with a clinically meaningful increase in raw score of ≥ 4 points or 10% from baseline (improved). The treatment period is 36 months. For all subjects who finish the subject and for those who discontinue, there will be a 30-day (± 15 days) and a 90-day (± 10 days) Safety Follow-up Visit. There is no planned protocol extension following the end of the study. Approximately 250 subjects with RMS will be recruited for this study. Subjects with RMS will be enrolled in this study if they have received ≤ 1 DMT, have an EDSS ≤ 3.5, and have been diagnosed with RMS within 5 years of study entry. The Investigator will be responsible for the overall conduct of the study at the site, confirmation of subject eligibility, routine study subject clinical management including for MS relapses, and management of AEs.

Official Title
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A Multicenter, Longitudinal, Open-Label, Single-Arm Study Describing Cognitive Processing Speed Changes in Relapsing Multiple Sclerosis Subjects Treated With Ozanimod (RPC-1063)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: RPC-1063


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Below are some criteria for inclusion. Additional Inclusion criteria apply. Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. Subject is male or female 18 to 65 years of age (inclusive) at the time of signing of the ICF. Subject has a diagnosis of MS according to the 2010 or 2017 Revised McDonald criteria. Subjects has ≤ 5 years since time of RMS diagnosis. Subject has ≤ 1 approved RMS DMT at time of study entry. Exclusion Criteria: Following are some criteria that would exclude the subject from participation. Additional exclusion criteria apply. Exclusions Related to General Health Subject has any clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study. Subjects with mild or moderate asthma, and subjects with other mild pulmonary disease (eg, chronic obstructive pulmonary disease [COPD]) may be included in the study. Subject has a presence of other neurologic disorders to explain the progressive neurologic disability (as defined in the key inclusion criteria) or that might affect cognition. Subject has a visual or other sensorimotor impairment likely to confound test performance. Subject has a presence of > 10 GdE lesions on the Baseline brain MRI scan. Subject has a history of developmental disorder (eg, attention-deficit/hyperactivity disorder [ADHD], learning disability).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of RPC-1063<br>Patients with relapsing MS will receive RPC-1063 orally: | Drug: RPC-1063<br>* Oral capsule<br>* Other names: Ozanimod;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with an increase in raw score of ≥ 4 points or 10% from baseline (improved) | Symbol Digit Modalities Test | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a decrease in raw score of ≥ 4 points or 10% from baseline (worsened) | Symbol Digit Modalities Test | Up to approximately 3 years | 
| Proportion of subjects with a raw score change from baseline who do not meet the improved or worsened definition (stable) | Symbol Digit Modalities Test | Up to approximately 3 years | 
| Proportion of subjects with an increase in raw score of ≥ 3 points from baseline | Symbol Digit Modalities Test | Up to approximately 3 years | 
| Proportion of subjects with a decrease in raw score of ≥ 3 points from baseline | Symbol Digit Modalities Test | Up to approximately 3 years | 
| Change from baseline in Symbol Digit Modalities Test (SMDT) | The SDMT is a measure of cognitive processing speed | Up to approximately 3 years | 
| Percent change from baseline in thalamic, cortical grey matter, whole brain, lateral ventricular, and MOV volumes | Magnetic resonance imaging (MRI) brain volume | Up to approximately 3 years | 
| Proportion of subjects free of gadolinium enhancing (GdE) lesions over 3 years | Magnetic Resonance Imaging | Up to approximately 3 years | 
| GdE lesion volume over 3 years | Magnetic Resonance Imaging | Up to approximately 3 years | 
| Number of unique new or enlarging hyperintense T2-weighted lesions and their volume from baseline to Year 3 | Magnetic Resonance Imaging | Up to approximately 3 years | 
| Number of unique new or enlarging hypointense T1 weighted lesions and their volume from baseline to Year 3 | Magnetic Resonance Imaging | Up to approximately 3 years | 
| Treatment Satisfaction Questionnaire for Medication (TSQM v1.4) | Change is TSQM score over 3 years | Up to approximately 3 years | 
| Work Productivity and Activity Impairment-Multiple Sclerosis (WPAI-MS) | Change in WPAI score over 3 years | Up to approximately 3 years | 
| Fatigue Severity Scale (FSS) | The Fatigue Severity Scale (FSS) questionnaire contains nine statements that attempt to explore severity of fatigue symptoms. | Up to approximately 3 years | 
| Multiple Sclerosis Quality of Life-54 (MSQOL-54) | The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument | Up to approximately 3 years | 
| Hospital Anxiety and Depression Scale (HADS) | The HADS was developed to identify anxiety disorders and depression among subjects in nonpsychiatric hospital clinics | Up to approximately 3 years | 
| Annualized relapse rate (ARR) | Change in relapse rate over 3 years | Up to approximately 3 years | 
| Timed 25-foot Walk (T25W) | Disability progression assessed by 20% worsening from baseline over 3 years on T25W | Up to approximately 3 years | 
| Nine-hole Peg Test (9-HPT) | Change from baseline in the time in seconds needed to complete test activity | Up to approximately 3 years | 
| Expanded Disability Status Scale (EDSS) | Change from baseline in EDSS score (0-10) yearly and at 3 years | Up to approximately 3 years | 
| Adverse Events (AEs) | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE. | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, RPC-1063, Ozanimod, Phase 3b