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

• ClinicalTrials.gov Identifier: NCT02294058
• Recruitment Status: Completed
• First Posted: November 19, 2014
• Results First Posted: November 25, 2020
• Last Update Posted: November 25, 2020
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: August 5, 2014
• First Posted Date: November 19, 2014
• Results First Submitted Date: December 22, 2017
• Results First Posted Date: November 25, 2020
• Last Update Posted Date: November 25, 2020
• Actual Study Start Date: December 3, 2014
• Actual Primary Completion Date: December 22, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2020)

Adjusted Annualized Relapse Rate (ARR) During the Treatment Period [ Time Frame: 12 months ]

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.

• Original Primary Outcome Measures (submitted: November 14, 2014): Annualized relapse rate [ Time Frame: 12 - 30 Months ]

Current Secondary Outcome Measures (submitted: November 23, 2020)

• Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months [ Time Frame: 12 month treatment period; MRI scans were assessed at Month 6 and Month 12 ]
  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.
• Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12 [ Time Frame: Month 12 ]
• Time to Onset of Disability Progression Confirmed After 3 Months [ Time Frame: From first dose to the end of the 12-month treatment period ]
  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.
• Time to Onset of Disability Progression Confirmed After 6 Months [ Time Frame: From first dose to the end of the 12-month treatment period ]
  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.
• Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12 [ Time Frame: Month 12 ]
  MRI scans were analyzed by blinded centralized reading facility.
• Percentage of Participants Who Were T2 Lesion-Free at Month 12 [ Time Frame: Month 12 ]
  MRI scans were analyzed by blinded centralized reading facility.
• Percent Change From Baseline in Normalized Brain Volume at Month 12 [ Time Frame: Baseline to Month 12 ]
  Brain volume (a measure of brain atrophy) was analyzed by MRI.
• Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test [ Time Frame: Baseline to Month 12 ]
  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.
• Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores [ Time Frame: Baseline to Month 12 ]
  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.
• Number of Participants With Treatment Emergent Adverse Events [ Time Frame: 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. ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Ozanimod (RPC1063) in Relapsing Multiple Sclerosis (MS)
• 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
• Brief Summary: The purpose of this study is to determine whether ozanimod is effective in the treatment of relapsing multiple sclerosis (RMS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Drug: Ozanimod
  Capsules for oral administration once a day
  Other Names:

  • RPC1063
  • Zeposia®
• Drug: Interferon beta-1a
  Administered by intramuscular injection once a week
  Other Names:

  • Avonex®
  • IFN β-1a
• Drug: Placebo to ozanimod
  Matching placebo capsules administered orally once a day
• Drug: Placebo to interferon beta-1a
  Placebo intramuscular injection once a week

Study Arms

• Active Comparator: Interferon beta-1a
  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.
  Interventions:

  • Drug: Interferon beta-1a
  • Drug: Placebo to ozanimod
• Experimental: Ozanimod 0.5 mg
  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.
  Interventions:

  • Drug: Ozanimod
  • Drug: Placebo to interferon beta-1a
• Experimental: Ozanimod 1 mg
  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.
  Interventions:

  • Drug: Ozanimod
  • Drug: Placebo to interferon beta-1a

Publications *

• Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdová E, Cree BAC, Sheffield JK, Minton N, Raghupathi K, Ding N, Cohen JA; SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019 Nov;18(11):1009-1020. doi: 10.1016/S1474-4422(19)30239-X. Epub 2019 Sep 3.
• Cree B, et al. The RADIANCE and SUNBEAM phase 3 studies of ozanimod in relapsing multiple sclerosis: study design and baseline characteristics. Presented at the 69th Annual American Academy of Neurology Meeting, April 22-28, 2017, Boston, MA. Abstract No. P6-344
• DeLuca J, Schippling S, Montalban X, Kappos L, Cree BAC, Comi G, Arnold DL, Hartung HP, Sheffield JK, Liu H, Silva D, Cohen JA. Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS. Mult Scler Relat Disord. 2021 Feb;48:102673. doi: 10.1016/j.msard.2020.102673. Epub 2020 Dec 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 4, 2017): 1346
• Original Estimated Enrollment (submitted: November 14, 2014): 1200
• Actual Study Completion Date: December 22, 2016
• Actual Primary Completion Date: December 22, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czechia, Estonia, Georgia, Germany, Hungary, Latvia, Lithuania, Moldova, Republic of, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Ukraine, United Kingdom, United States
• Removed Location Countries: Argentina, Austria, Colombia, Czech Republic, Mexico, Peru

Administrative Information

• NCT Number: NCT02294058
• Other Study ID Numbers: RPC01-301; 2014-002320-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Celgene
• Study Sponsor: Celgene
• Collaborators: Not Provided

Investigators

• Study Director: James Sheffiled, MD; Celgene

• PRS Account: Celgene
• Verification Date: November 2020