A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of the trial is to determine the safety and efficacy of RPC1063 in patients with relapsing multiple sclerosis.

Detailed Description
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The trial is an open label extension study. Eligible patients from the RPC01-201, RPC01-301, and RPC01-1001 trials diagnosed with relapsing Multiple Sclerosis (RMS) will be enrolled to receive study drug until the end of the trial or until the Sponsor discontinues the development program.

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: RPC1063


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: To be eligible to participate in this trial, patients must meet all of the following criteria: Completed one of the parent trials Does not have a condition that would require withdrawal from one of the parent trials Has no conditions requiring treatment with a prohibited concomitant medication Is not receiving treatment with any of the following drugs or interventions within the corresponding timeframe: At Baseline (Day 1) CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin) Two weeks prior to Baseline (Day 1) Monoamine oxidase inhibitors (eg, selegiline, phenelzine) Ability to provide written informed consent and to be compliant with the schedule of protocol assessments Female patients of childbearing potential: Must agree to practice a highly effective method of contraception throughout the study until completion of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. Acceptable methods of birth control in this study are the following: Combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable Placement of an intrauterine device (IUD) Placement of an intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomised partner Sexual abstinence. Exclusion Criteria:

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 mg RPC1063 (Ozanimod) oral capsule<br>1 mg RPC1063 (Ozanimod) oral capsule daily | Drug: RPC1063<br> <br> * Other names: Ozanimod;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Safety and tolerability characterized by the incidence, relationship, and type of adverse events, serious adverse events, and adverse events leading to withdrawal from the trial as well as the incidence, relationship, and type of laboratory abnormalities, vital signs changes, electrocardiogram results, and physical examination abnormalities. | Up to approximately 7 years | 
| Suicidality will be assessed in the trial | Suicidality will be assessed with the C-SSRS (Columbia-Suicide Severity Rating Scale) throughout the trial and post study drug safety follow-up. | Up to approximately 7 years | 
| Adverse events of special interest (AESIs) | AESIs potentially associated with the pharmacologic effects of S1P modulators (ophthalmologic, cardiac, hepatic, infections, pulmonary, malignancy) | Up to approximately 7 years | 
| Dependence and withdrawal assessment - Physician's Withdrawal Checklist (PWC-20) in 80 participants who discontinue study drug | The Physician's Withdrawal Checklist (PWC-20) is a rater-administered 20-item scale to assess signs and symptoms of withdrawal. Changes from last on study-drug assessment to post study drug Day 1, 4, 7, 14, 21, 90 will be summarized | Up to approximately 7 years | 
| Dependence and withdrawal assessment - Hospital Anxiety and Depression Scale (HADS) in 80 participants who discontinue study drug | The HADS is a validated patient reported outcome for assessing anxiety and depression (Zigmond 1983; Bjelland 2002). It consists of 7 items related to anxiety and 7 items related to depression. Changes from last on study-drug assessment to post study drug Day 1, 4, 7, 14, 21, 90 will be summarized | Up to approximately 7 years | 
| Dependence and withdrawal assessment - Epworth Sleepiness Scale (ESS) in 80 participants who discontinue study drug | The ESS is a validated self-administered questionnaire with 8 questions (Johns 1997), where higher scores indicate more daytime sleepiness. Changes from last on study-drug assessment to post study drug Day 1, 4, 7, 14, 21, 90 will be summarized. | Up to approximately 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized relapse rate | Annualized relapse rate is based on relapses that were confirmed by the treating investigator to meet the protocol-defined definition of relapse A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. Confirmed relapses are accompanied by a change in EDSS. The adjusted annualized relapse rate will be the primary efficacy endpoint estimated using a negative binomial regression model adjusted for region, age at Baseline, and the Baseline number of GdE lesions, and included the natural log transformation of time on study as an offset term. | Up to approximately 7 years | 
| Time to first relapse | Time to first relapse will be analyzed using Kaplan-Meier methods The estimated median time to relapse will be reported along with the associated 95% CI (or NE without a CI if the median is not estimable). | Up to approximately 7 years | 
| The number of new or enlarging hyperintense T2-weighted brain magnetic resonance imaging lesions at each visit | The total number of new or enlarging hyperintense T2-weighted brain magnetic resonance imaging lesions at each visit will be collected and summarized by treatment group using descriptive statistics, counts, and percentages | Up to approximately 7 years | 
| The number of gadolinium-enhanced brain magnetic resonance imaging lesions at each visit | The total number gadolinium-enhanced brain magnetic resonance imaging lesions at each visit will be collected and summarized using counts and percentages. | Up to approximately 7 years | 
| Time to onset of disability progression as defined by a sustained worsening in Expanded Disability Status Scale (EDSS) of 1.0 points or more from baseline | Sustained disability progression is defined as at least a 1.0 point increase on the EDSS score from the reference (Parent or OLE) Baseline, confirmed after a 3 month and a 6 month period. Confirmation of MS disease progression must not occur at the time of a relapse. | Up to approximately 7 years | 
| Proportion of patients who are free of gadolinium-enhanced lesions at each visit | The proportion of patients who are free of gadolinium-enhanced lesions at each visit will be collected and reported. | Up to approximately 7 years | 
| Proportion of patients who are free of new or enlarging T2 lesions at each visit | The proportion of patients who are free of new or enlarging T2 lesions at each visit will be collected and reported. | Up to approximately 7 years | 
| Normalized Brain Volume, Cortical Grey Matter and Thalamic Volume Loss | Percent change of brain volume, cortical grey matter volume and thalamic volume will be reported referencing parent baseline in parent studies and OLE. The percent change of the three brain atrophy assessments will be summarized using descriptive statistics by treatment group. | Up to approximately 7 years | 
| Multiple Sclerosis Functional Composite (MSFC) and MSFC plus the Low-Contrast Letter Acuity Test (LCLA)) | The Multiple Sclerosis Functional Composite (MSFC) (Cutter 1999) is a composite measure assessing upper extremity function, ambulation and cognition. The Low-Contrast Letter Acuity Test (LCLA) is performed with the MSFC assessments and assesses for disturbances in visual function seen in patients with MS . The change in MSFC and MSFC + LCLA score from Baseline at each applicable visit will be collected and reported. | Up to approximately 7 years | 
| Multiple Sclerosis Quality of Life 54 | The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument (Vickrey 1995). The change in Multiple Sclerosis Quality of Life 54 score from Baseline at each applicable visit will be collected and reported. | Up to approximately 7 years | 
| Changes in other magnetic resonance imaging variables including number and volume of gadolinium-enhanced T1 lesions, volume of T2 lesions, number of new or enlarging T2 lesions, volume of unenhancing T1 lesions, number of new unenhancing T1 lesions | The changes in other magnetic resonance imaging variables including number and volume of gadolinium-enhanced T1 lesions, volume of T2 lesions, number of new or enlarging T2 lesions, volume of unenhancing T1 lesions, number of new unenhancing T1 lesions will be collected and reported. | Up to approximately 7 years | 

 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