Back to resultsA Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
RPC1063
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring MS, RMS, Multiple Sclerosis, Relapsing Multiple Sclerosis
Eligibility Criteria
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:
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1 mg RPC1063 (Ozanimod) oral capsule
Arm Description
1 mg RPC1063 (Ozanimod) oral capsule daily
Outcomes
Primary Outcome Measures
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.
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.
Adverse events of special interest (AESIs)
AESIs potentially associated with the pharmacologic effects of S1P modulators (ophthalmologic, cardiac, hepatic, infections, pulmonary, malignancy)
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
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
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.
Secondary Outcome Measures
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.
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).
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
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02576717
Brief Title
A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
October 16, 2015 (Actual)
Primary Completion Date
January 5, 2023 (Actual)
Study Completion Date
January 5, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the trial is to determine the safety and efficacy of RPC1063 in patients with relapsing multiple sclerosis.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
MS, RMS, Multiple Sclerosis, Relapsing Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2350 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1 mg RPC1063 (Ozanimod) oral capsule
Arm Type
Experimental
Arm Description
1 mg RPC1063 (Ozanimod) oral capsule daily
Intervention Type
Drug
Intervention Name(s)
RPC1063
Other Intervention Name(s)
Ozanimod
Primary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
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.
Time Frame
Up to approximately 7 years
Title
Suicidality will be assessed in the trial
Description
Suicidality will be assessed with the C-SSRS (Columbia-Suicide Severity Rating Scale) throughout the trial and post study drug safety follow-up.
Time Frame
Up to approximately 7 years
Title
Adverse events of special interest (AESIs)
Description
AESIs potentially associated with the pharmacologic effects of S1P modulators (ophthalmologic, cardiac, hepatic, infections, pulmonary, malignancy)
Time Frame
Up to approximately 7 years
Title
Dependence and withdrawal assessment - Physician's Withdrawal Checklist (PWC-20) in 80 participants who discontinue study drug
Description
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
Time Frame
Up to approximately 7 years
Title
Dependence and withdrawal assessment - Hospital Anxiety and Depression Scale (HADS) in 80 participants who discontinue study drug
Description
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
Time Frame
Up to approximately 7 years
Title
Dependence and withdrawal assessment - Epworth Sleepiness Scale (ESS) in 80 participants who discontinue study drug
Description
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.
Time Frame
Up to approximately 7 years
Secondary Outcome Measure Information:
Title
Annualized relapse rate
Description
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.
Time Frame
Up to approximately 7 years
Title
Time to first relapse
Description
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).
Time Frame
Up to approximately 7 years
Title
The number of new or enlarging hyperintense T2-weighted brain magnetic resonance imaging lesions at each visit
Description
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
Time Frame
Up to approximately 7 years
Title
The number of gadolinium-enhanced brain magnetic resonance imaging lesions at each visit
Description
The total number gadolinium-enhanced brain magnetic resonance imaging lesions at each visit will be collected and summarized using counts and percentages.
Time Frame
Up to approximately 7 years
Title
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
Description
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.
Time Frame
Up to approximately 7 years
Title
Proportion of patients who are free of gadolinium-enhanced lesions at each visit
Description
The proportion of patients who are free of gadolinium-enhanced lesions at each visit will be collected and reported.
Time Frame
Up to approximately 7 years
Title
Proportion of patients who are free of new or enlarging T2 lesions at each visit
Description
The proportion of patients who are free of new or enlarging T2 lesions at each visit will be collected and reported.
Time Frame
Up to approximately 7 years
Title
Normalized Brain Volume, Cortical Grey Matter and Thalamic Volume Loss
Description
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.
Time Frame
Up to approximately 7 years
Title
Multiple Sclerosis Functional Composite (MSFC) and MSFC plus the Low-Contrast Letter Acuity Test (LCLA))
Description
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.
Time Frame
Up to approximately 7 years
Title
Multiple Sclerosis Quality of Life 54
Description
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.
Time Frame
Up to approximately 7 years
Title
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
Description
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.
Time Frame
Up to approximately 7 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
12. IPD Sharing Statement
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
http://www.BMSStudyConnect.com
Description
BMS Clinical Trial Patient Recruiting
Learn more about this trial
A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
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