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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: RPC-1063

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Halifax, Canada, B3R 1V9
    • Local Institution - 207
  • Ontario
    • London, Ontario, Canada, N6G 2V4
      • Local Institution - 203
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 204
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Local Institution - 206
• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Local Institution - 166
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Local Institution - 123
    • Cullman, Alabama, United States, 35058
      • Local Institution - 136
    • Mobile, Alabama, United States, 36617
      • Local Institution - 153
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Local Institution - 162
  • California
    • Pasadena, California, United States, 91105
      • Local Institution - 128
    • Sacramento, California, United States, 95817
      • Local Institution - 164
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 107
    • Colorado Springs, Colorado, United States, 80907
      • Local Institution - 102
    • Fort Collins, Colorado, United States, 80528
      • Local Institution - 144
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 109
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Local Institution - 140
    • Vero Beach, Florida, United States, 32960-4818
      • Local Institution - 158
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Local Institution - 114
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Northwest Neurology, Ltd
    • Northbrook, Illinois, United States, 60062
      • Local Institution - 108
  • Indiana
    • Fort Wayne, Indiana, United States, 46825-1603
      • Local Institution - 148
  • Iowa
    • Ames, Iowa, United States, 50010
      • Local Institution - 126
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Local Institution - 173
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Local Institution - 133
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 152
    • Detroit, Michigan, United States, 48202
      • Local Institution - 112
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 122
    • Saint Louis, Missouri, United States, 63131
      • Local Institution - 143
  • Montana
    • Great Falls, Montana, United States, 59405
      • Advanced Neurology Specialists
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Local Institution - 149
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Buffalo, New York, United States, 14202
      • Local Institution - 137
    • East Setauket, New York, United States, 11733-3528
      • Local Institution - 160
    • New York, New York, United States, 10016
      • Local Institution - 130
    • New York, New York, United States, 10021
      • Local Institution - 121
    • Patchogue, New York, United States, 11772
      • Local Institution - 146
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Local Institution - 131
    • Greensboro, North Carolina, United States, 27405
      • Local Institution - 106
    • Mooresville, North Carolina, United States, 28117
      • Local Institution - 170
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates PA
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Local Institution - 174
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 171
    • Dayton, Ohio, United States, 45417
      • UC Health, Llc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Local Institution - 157
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Local Institution - 159
    • Philadelphia, Pennsylvania, United States, 19140
      • Local Institution - 169
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Magee Womens Hospital
  • Tennessee
    • Franklin, Tennessee, United States, 37064
      • Local Institution - 125
    • Knoxville, Tennessee, United States, 37922
      • Local Institution - 119
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute - Dallas Clinical Trials Office
    • Round Rock, Texas, United States, 78681
      • Local Institution - 113
    • San Antonio, Texas, United States, 78259
      • Local Institution - 101
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 103
  • Washington
    • Kirkland, Washington, United States, 98034
      • Local Institution - 141
    • Seattle, Washington, United States, 98101
      • Local Institution - 168
    • Spokane, Washington, United States, 99202
      • Local Institution - 172
    • Tacoma, Washington, United States, 98405
      • Local Institution - 124
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Local Institution - 156
    • Morgantown, West Virginia, United States, 26506
      • Local Institution - 150
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Local Institution - 167
    • Milwaukee, Wisconsin, United States, 53226
      • Local Institution - 147

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Below are some criteria for inclusion. Additional Inclusion criteria apply.

1. Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
2. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
3. Subject is male or female 18 to 65 years of age (inclusive) at the time of signing of the ICF.
4. Subject has a diagnosis of MS according to the 2010 or 2017 Revised McDonald criteria.
5. Subjects has ≤ 5 years since time of RMS diagnosis.
6. 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

1. 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.
2. 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.
3. Subject has a visual or other sensorimotor impairment likely to confound test performance.
4. Subject has a presence of > 10 GdE lesions on the Baseline brain MRI scan.
5. Subject has a history of developmental disorder (eg, attention-deficit/hyperactivity disorder [ADHD], learning disability).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of RPC-1063; Patients with relapsing MS will receive RPC-1063 orally:	Drug: RPC-1063; Oral capsule; Other Names: Ozanimod

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Estimated): January 27, 2026
• Study Completion (Estimated): April 27, 2026

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Ozanimod; Phase 3b; RPC-1063
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Ozanimod
• Other Study ID Numbers: RPC-1063-MS-001; U1111-1240-5667 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No