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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Ozanimod
Drug: Interferon beta-1a
Drug: Placebo to ozanimod
Drug: Placebo to interferon beta-1a
Enrollment 1346
Recruitment Details The study was conducted at 152 sites in 20 countries in Eastern and Western Europe, the United States, and New Zealand. Between December 2014 and November 2015, 1656 participants were screened, of whom 1346 were eligible and enrolled.
Pre-assignment Details Participants were randomly assigned to one of three treatment groups in a 1:1:1 ratio. Randomization was stratified by Baseline Expanded Disability Status Scale (EDSS) score (≤ 3.5, > 3.5) and country.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description Participants received 30 µg interferon beta-1a (IFN β-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 at least 12 months. Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection (identical in appearance to Interferon) weekly until the last participant had been treated for at least 12 months. Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection (identical in appearance to Interferon) weekly until the last participant had been treated for at least 12 months.
Period Title: Overall Study
Started 448 451 447
Safety Population [1] 445 453 448
Completed 412 425 418
Not Completed 36 26 29
Reason Not Completed
Adverse Event             16             7             13
Lack of Efficacy             3             3             0
Lost to Follow-up             1             0             2
Withdrawal by Subject             10             14             13
Physician Decision             2             1             0
Miscellaneous             4             1             1
[1]
Three participants randomized to the interferon beta-1a group received ozanimod in error at some visits (2 participants received ozanimod 0.5 mg and 1 participant received ozanimod 1 mg) and are counted in the ozanimod groups in the Safety Population.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg Total
Hide Arm/Group Description Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months. Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months. Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months. Total of all reporting groups
Overall Number of Baseline Participants 448 451 447 1346
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants who received at least 1 dose of study drug; participants were analyzed according to the treatment they were randomized to receive and not according to what they actually received, if different.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
35.9  (9.11) 36.0  (9.43) 34.8  (9.24) 35.6  (9.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
Female
300
  67.0%
311
  69.0%
283
  63.3%
894
  66.4%
Male
148
  33.0%
140
  31.0%
164
  36.7%
452
  33.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
Black
0
   0.0%
2
   0.4%
0
   0.0%
2
   0.1%
Asian
0
   0.0%
1
   0.2%
1
   0.2%
2
   0.1%
White
447
  99.8%
447
  99.1%
446
  99.8%
1340
  99.6%
Other
1
   0.2%
1
   0.2%
0
   0.0%
2
   0.1%
Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
Rest of World
29
   6.5%
32
   7.1%
32
   7.2%
93
   6.9%
Eastern Europe
419
  93.5%
419
  92.9%
415
  92.8%
1253
  93.1%
[1]
Measure Description:

Eastern Europe includes Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Estonia, Georgia, Latvia, Lithuania, Moldova, Poland, Romania, Russia, Serbia, and Ukraine.

Rest of world includes the United States, Germany, Portugal, Spain, Sweden, and New Zealand.

Expanded Disability Status Scale (EDSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
2.62  (1.138) 2.65  (1.135) 2.61  (1.160) 2.62  (1.144)
[1]
Measure Description: The EDSS is a scale for quantifying disability in MS. Eight functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored on a scale of 0 (no disability) to 5 or 6 (more severe disability). Ambulation is also scored. Based on scores in these 8 functional systems and gait, an overall score ranging from 0 (normal) to 10 (death due to MS) in 0.5 unit increments is assigned. Participants with EDSS scores of 0.0 to 4.5 are fully ambulatory; patients with EDSS scores of 5.0 to 9.5 have impaired ambulation.
Time Since MS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
6.88  (5.877) 7.16  (6.255) 6.85  (6.449) 6.96  (6.195)
Time Since MS Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
3.71  (4.361) 3.70  (4.518) 3.60  (4.193) 3.67  (4.357)
Age at MS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
29.5  (8.92) 29.3  (9.25) 28.4  (8.42) 29.1  (8.88)
Age at MS Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 448 participants 451 participants 447 participants 1346 participants
32.7  (9.01) 32.7  (9.49) 31.6  (8.81) 32.4  (9.12)
1.Primary Outcome
Title Adjusted Annualized Relapse Rate (ARR) During the Treatment Period
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants who received at least 1 dose of study medication.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 447
Least Squares Mean (95% Confidence Interval)
Unit of Measure: relapses/year
0.350
(0.279 to 0.440)
0.241
(0.188 to 0.308)
0.181
(0.140 to 0.236)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.025 level.
Method Poisson regression model
Comments Adjusted for region, Baseline age, number of gadolinium enhancing (GdE) lesions and included the natural log transformation of time as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.518
Confidence Interval (2-Sided) 95%
0.405 to 0.663
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.025 level.
Method Poisson Regression Model
Comments Adjusted for region, Baseline age and the number of GdE lesions, and included the natural log transformation of time on study as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.688
Confidence Interval (2-Sided) 95%
0.547 to 0.864
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months
Hide Description 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.
Time Frame 12 month treatment period; MRI scans were assessed at Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants with non-missing MRI results.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 382 397 388
Least Squares Mean (95% Confidence Interval)
Unit of Measure: T2 lesions/scan
2.836
(2.331 to 3.451)
2.139
(1.777 to 2.575)
1.465
(1.203 to 1.784)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.05 level.
Method Negative Binomial Regression Model
Comments Adjusted for region, Baseline age and GdE lesions; included the natural log transformation of available MRI scans over 12 months as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.517
Confidence Interval (2-Sided) 95%
0.427 to 0.625
Estimation Comments Rate Ratio = Ozanimod / IFN β-1a
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.05 level.
Method Negative binomial regression model
Comments Adjusted for region, Baseline age and GdE lesions; included the natural log transformation of available MRI scans over 12 months as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.754
Confidence Interval (2-Sided) 95%
0.625 to 0.910
Estimation Comments Rate Ratio = Ozanimod / IFN β-1a
3.Secondary Outcome
Title Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12
Hide Description [Not Specified]
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants with non-missing MRI results.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 382 397 388
Least Squares Mean (95% Confidence Interval)
Unit of Measure: lesions
0.433
(0.295 to 0.635)
0.287
(0.197 to 0.418)
0.160
(0.106 to 0.242)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.05 level.
Method Negative Binomial Regression Model
Comments Adjusted for region, Baseline age and GdE lesions; included the natural log transformation of available MRI scans as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.370
Confidence Interval (2-Sided) 95%
0.256 to 0.536
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0182
Comments To account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.05 level.
Method Negative binomial regression model
Comments Adjusted for region, Baseline age and GdE lesions; included the natural log transformation of available MRI scans as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.662
Confidence Interval (2-Sided) 95%
0.471 to 0.932
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Onset of Disability Progression Confirmed After 3 Months
Hide Description

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 Frame From first dose to the end of the 12-month treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 447
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimable as there were insufficient disability events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3055
Comments [Not Specified]
Method Cox proportional hazards model
Comments Based on the Cox proportional hazard model with factors for treatment group, adjusted for region, Baseline age, and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.690
Confidence Interval (2-Sided) 95%
0.340 to 1.402
Estimation Comments Hazard Ratio (Ozanimod / IFN β-1a)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7163
Comments [Not Specified]
Method Cox proportional hazards model
Comments Based on the Cox proportional hazard model with factors for treatment group, adjusted for region, Baseline age and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.886
Confidence Interval (2-Sided) 95%
0.460 to 1.705
Estimation Comments Hazard Ratio (Ozanimod / IFN β-1a)
5.Secondary Outcome
Title Time to Onset of Disability Progression Confirmed After 6 Months
Hide Description

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.

Time Frame From first dose to the end of the 12-month treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 447
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimable as there were insufficient disability events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6725
Comments [Not Specified]
Method Cox proportional hazards model
Comments Based on the Cox proportional hazard model with factors for treatment group, adjusted for region, Baseline age and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.238
Confidence Interval (2-Sided) 95%
0.460 to 3.337
Estimation Comments Hazard Ratio (Ozanimod / IFN β-1a)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3755
Comments [Not Specified]
Method Cox proportional hazard model
Comments Based on the Cox proportional hazard model with factors for treatment group, adjusted for region, Baseline age and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.535
Confidence Interval (2-Sided) 95%
0.595 to 3.963
Estimation Comments Hazard Ratio (Ozanimod / IFN β-1a)
6.Secondary Outcome
Title Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12
Hide Description MRI scans were analyzed by blinded centralized reading facility.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population; Participants who were missing the Month 12 MRI data were considered non-responders; ie, as not being lesion-free (non-responder imputation).
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 447
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.17
(58.70 to 67.64)
68.29
(64.00 to 72.59)
74.05
(69.99 to 78.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the CMH test stratified by region and EDSS category per Interactive Voice Response System (IVRS)
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 10.88
Confidence Interval (2-Sided) 95%
4.84 to 16.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1130
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the CMH test stratified by region and EDSS category per IVRS.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 5.12
Confidence Interval (2-Sided) 95%
-1.07 to 11.32
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Who Were T2 Lesion-Free at Month 12
Hide Description MRI scans were analyzed by blinded centralized reading facility.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population; participants who were missing the Month 12 MRI data were considered non-responders, ie, as not being lesion-free.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 447
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
23.44
(19.51 to 27.36)
26.39
(22.32 to 30.45)
27.96
(23.80 to 32.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1180
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the CMH test stratified by region and EDSS Scale category per IVRS.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 4.53
Confidence Interval (2-Sided) 95%
-1.19 to 10.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3023
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the CMH test stratified by region and EDSS Scale category per IVRS.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
-2.70 to 8.60
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Normalized Brain Volume at Month 12
Hide Description Brain volume (a measure of brain atrophy) was analyzed by MRI.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population with available MRI data at Baseline and Month 12
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 334 347 338
Median (Full Range)
Unit of Measure: percent change
-0.57
(-3.7 to 1.1)
-0.50
(-2.7 to 1.4)
-0.39
(-2.8 to 2.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments Due to the non-normal distribution of the data for brain volume loss, the analyses for percent change from baseline in normalized brain volume were compared using rank-ANCOVA, adjusted for region (Eastern Europe vs Rest of World), and EDSS category per IVRS, with the dependent variable as the residual of the rank of brain volume at Baseline regressed on rank of percent change.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Rank ANCOVA
Comments Adjusted for region and EDSS category per IVRS
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments Due to the non-normal distribution of the data for brain volume loss, the analyses for percent change from baseline in normalized brain volume were compared using rank-ANCOVA, adjusted for region (Eastern Europe vs Rest of World), and EDSS category per IVRS, with the dependent variable as the residual of the rank of brain volume at Baseline regressed on rank of percent change.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0615
Comments [Not Specified]
Method Rank ANCOVA
Comments Adjusted for region and EDSS Scale per IVRS
9.Secondary Outcome
Title Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test
Hide Description

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.

Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population with available Baseline and Month 12 MSFC z-scores.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 447 450 447
Mean (Standard Deviation)
Unit of Measure: z-score
-0.022  (0.334) -0.007  (0.351) 0.003  (0.328)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1290
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS and the Baseline MSFC score.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.034
Confidence Interval (2-Sided) 95%
-0.010 to 0.077
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4942
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS and the Baseline MSFC score
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.015
Confidence Interval (2-Sided) 95%
-0.028 to 0.059
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores
Hide Description

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.

Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with available Baseline data; missing post-baseline data were imputed using a mixed-effects regression model (random slope and intercept).
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 448 451 446
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical health composite summary Number Analyzed 445 participants 448 participants 443 participants
0.046  (12.578) 1.414  (12.343) 1.925  (11.870)
Mental health composite summary Number Analyzed 448 participants 451 participants 446 participants
-0.123  (15.240) 0.283  (15.686) 0.260  (15.800)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments Analysis of Physical Health Composite Summary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0364
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS, and the Baseline summary score.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.642
Confidence Interval (2-Sided) 95%
0.104 to 3.180
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments Analysis of Physical Health Composite Summary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1905
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS, and the Baseline summary score.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.024
Confidence Interval (2-Sided) 95%
-0.510 to 2.559
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments Analysis of Mental Health Composite Summary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7104
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS, and the Baseline summary score.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.356
Confidence Interval (2-Sided) 95%
-1.523 to 2.234
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments Analysis of Mental Health Composite Summary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8587
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for region, EDSS category per IVRS, and the Baseline summary score.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.170
Confidence Interval (2-Sided) 95%
-2.045 to 1.705
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants who received at least 1 dose of randomized study medication, analyzed according to the highest dose of ozanimod treatment actually received (up to 1 mg) and not according to the treatment they were randomized to receive, if different.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
Overall Number of Participants Analyzed 445 453 448
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
336
  75.5%
259
  57.2%
268
  59.8%
Any Moderate or Severe TEAE
182
  40.9%
113
  24.9%
138
  30.8%
Any Severe TEAE
10
   2.2%
10
   2.2%
7
   1.6%
Any Suspected TEAE
83
  18.7%
76
  16.8%
91
  20.3%
Any Related TEAE
13
   2.9%
8
   1.8%
7
   1.6%
Any Serious TEAE
11
   2.5%
16
   3.5%
13
   2.9%
Any Suspected Serious TEAE
0
   0.0%
0
   0.0%
3
   0.7%
Any Related Serious TEAE
0
   0.0%
0
   0.0%
1
   0.2%
Any TEAE Leading to Stopping of Study Drug
16
   3.6%
7
   1.5%
13
   2.9%
Any TEAE Leading to Study Withdrawal
16
   3.6%
7
   1.5%
13
   2.9%
Any Death
0
   0.0%
0
   0.0%
0
   0.0%
Any Death related to Study Drug
0
   0.0%
0
   0.0%
0
   0.0%
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.
Adverse Event Reporting Description The Safety population included all participants who received at least 1 dose of randomized study drug. All participants in the Safety population were analyzed according to the highest dose of ozanimod treatment actually received (up to 1 mg) and not according to the treatment they were randomized to receive, if different.
 
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description Participants received 30 µg interferon beta-1a by IM injection weekly and matching placebo capsules orally once a day until the last participant had been treated for at least 12 months. Participants received ozanimod 0.5 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months. Participants received ozanimod 1 mg orally once a day and a placebo intramuscular injection weekly until the last participant had been treated for at least 12 months.
All-Cause Mortality
Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/445 (2.47%)   16/453 (3.53%)   13/448 (2.90%) 
Cardiac disorders       
Atrial Fibrillation  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Sinus Bradycardia  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Supraventricular Tachycardia  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Gastrointestinal disorders       
Duodenal Ulcer  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Haemorrhoids  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Hepatobiliary disorders       
Gallbladder Polyp  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Infections and infestations       
Appendiceal Abscess  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Appendicitis  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Influenza  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Lyme Disease  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Postoperative Abscess  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Pyelonephritis Acute  1  1/445 (0.22%)  0/453 (0.00%)  1/448 (0.22%) 
Subcutaneous Abscess  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Urinary Tract Infection  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Injury, poisoning and procedural complications       
Ankle Fracture  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Eye Injury  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Facial Bones Fracture  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Subdural Haematoma  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Investigations       
Fibrin D Dimer Increased  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Intervertebral Disc Disorder  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal Cell Carcinoma  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Benign Ovarian Tumour  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Fibroadenoma Of Breast  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Invasive Breast Carcinoma  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Testicular Seminoma (Pure) Stage I  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Uterine Leiomyoma  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Nervous system disorders       
Cerebral Infarction  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Cervical Radiculopathy  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Multiple Sclerosis Relapse  1  2/445 (0.45%)  0/453 (0.00%)  0/448 (0.00%) 
Myelopathy  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Syncope  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Vascular Encephalopathy  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Pregnancy, puerperium and perinatal conditions       
Abortion Spontaneous  1  0/445 (0.00%)  0/453 (0.00%)  1/448 (0.22%) 
Psychiatric disorders       
Insomnia  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Renal and urinary disorders       
Renal Colic  1  0/445 (0.00%)  1/453 (0.22%)  1/448 (0.22%) 
Reproductive system and breast disorders       
Menometrorrhagia  1  1/445 (0.22%)  0/453 (0.00%)  0/448 (0.00%) 
Postmenopausal Haemorrhage  1  0/445 (0.00%)  1/453 (0.22%)  0/448 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   273/445 (61.35%)   88/453 (19.43%)   57/448 (12.72%) 
General disorders       
Influenza Like Illness  1  227/445 (51.01%)  18/453 (3.97%)  17/448 (3.79%) 
Pyrexia  1  28/445 (6.29%)  5/453 (1.10%)  5/448 (1.12%) 
Infections and infestations       
Nasopharyngitis  1  36/445 (8.09%)  44/453 (9.71%)  30/448 (6.70%) 
Upper Respiratory Tract Infection  1  24/445 (5.39%)  31/453 (6.84%)  18/448 (4.02%) 
Nervous system disorders       
Headache  1  25/445 (5.62%)  27/453 (5.96%)  34/448 (7.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than one (1) year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene sixty (60) days prior to submission. Celgene may remove confidential and/or proprietary information before publication
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: AMcClain@celgene.com
Publications of Results:
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
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02294058    
Other Study ID Numbers: RPC01-301
2014-002320-27 ( EudraCT Number )
First Submitted: August 5, 2014
First Posted: November 19, 2014
Results First Submitted: December 22, 2017
Results First Posted: November 25, 2020
Last Update Posted: November 25, 2020