Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety Study of Ozanimod in Relapsing Multiple Sclerosis (RADIANCE)

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: NCT02047734
Recruitment Status : Completed
First Posted : January 28, 2014
Results First Posted : February 11, 2021
Last Update Posted : February 11, 2021
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 Relapsing Multiple Sclerosis
Interventions Drug: Ozanimod
Drug: Ozanimod placebo
Drug: Interferon beta-1a
Drug: Interferon beta-1a placebo
Enrollment 1320
Recruitment Details The study was conducted at 147 academic medical centers and clinical practices in 21 countries in North America, Europe, and South Africa. Between December 2013 and March 2015, 1695 participants were screened, of which 375 did not meet inclusion criteria. One thousand, three hundred and twenty participants with relapsing multiple sclerosis (MS) were enrolled and randomly assigned to a treatment group.
Pre-assignment Details

Participants were randomized in a 1:1:1 ratio to one of three treatment groups. Randomization was stratified by Baseline Expanded Disability Status Scale (EDSS) score (≤ 3.5, > 3.5) and by country.

Participants who completed the 24-month study were eligible to enroll in a long-term, open-label extension study (RPC01-3001; NCT02576717).

Arm/Group Title Interferon Beta-1a (IFN β-1a) Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description Participants received interferon beta-1a (IFN β-1a) 30 µg intramuscular (IM) injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months. Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months. Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Period Title: Overall Study
Started 443 443 434
Received Treatment 441 [1] 439 [2] 433
Completed [3] 376 374 388
Not Completed 67 69 46
Reason Not Completed
Adverse Event             18             13             13
Lack of Efficacy             4             5             1
Protocol Violation             3             1             1
Lost to Follow-up             1             4             0
Death             0             1             0
Withdrawal by Subject             30             31             19
Physician Decision             7             6             5
Miscellaneous             2             4             6
Did Not Receive Study Drug             2             4             1
[1]
One participant received ozanimod 0.5 mg in error
[2]
One participant received ozanimod 1.0 mg in error
[3]
Completed study drug
Arm/Group Title Interferon Beta-1a (IFN β-1a) Ozanimod 0.5 mg Ozanimod 1 mg Total
Hide Arm/Group Description Participants received IFN β-1a 30 µg intramuscular (IM) injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months. Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months. Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months. Total of all reporting groups
Overall Number of Baseline Participants 441 439 433 1313
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included 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 441 participants 439 participants 433 participants 1313 participants
35.1  (9.07) 35.4  (8.82) 36.0  (8.89) 35.5  (8.93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
Female
304
  68.9%
287
  65.4%
291
  67.2%
882
  67.2%
Male
137
  31.1%
152
  34.6%
142
  32.8%
431
  32.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
Hispanic or Latino
5
   1.1%
6
   1.4%
10
   2.3%
21
   1.6%
Not Hispanic or Latino
436
  98.9%
433
  98.6%
423
  97.7%
1292
  98.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
White
432
  98.0%
431
  98.2%
428
  98.8%
1291
  98.3%
Black
7
   1.6%
6
   1.4%
5
   1.2%
18
   1.4%
Asian
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Other
1
   0.2%
2
   0.5%
0
   0.0%
3
   0.2%
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
North America
16
   3.6%
16
   3.6%
16
   3.7%
48
   3.7%
Western Europe
40
   9.1%
40
   9.1%
36
   8.3%
116
   8.8%
Eastern Europe
379
  85.9%
378
  86.1%
374
  86.4%
1131
  86.1%
Southern Africa
6
   1.4%
5
   1.1%
7
   1.6%
18
   1.4%
Country of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
Belarus
40
   9.1%
38
   8.7%
37
   8.5%
115
   8.8%
Belgium
4
   0.9%
4
   0.9%
4
   0.9%
12
   0.9%
Bosnia And Herzegovina
3
   0.7%
3
   0.7%
2
   0.5%
8
   0.6%
Bulgaria
11
   2.5%
12
   2.7%
11
   2.5%
34
   2.6%
Canada
1
   0.2%
1
   0.2%
0
   0.0%
2
   0.2%
Croatia
16
   3.6%
15
   3.4%
14
   3.2%
45
   3.4%
Georgia
12
   2.7%
11
   2.5%
13
   3.0%
36
   2.7%
Greece
3
   0.7%
4
   0.9%
2
   0.5%
9
   0.7%
Hungary
7
   1.6%
9
   2.1%
6
   1.4%
22
   1.7%
Italy
8
   1.8%
9
   2.1%
7
   1.6%
24
   1.8%
Poland
125
  28.3%
124
  28.2%
124
  28.6%
373
  28.4%
Republic of Moldova
2
   0.5%
4
   0.9%
3
   0.7%
9
   0.7%
Romania
9
   2.0%
9
   2.1%
10
   2.3%
28
   2.1%
Russian Federation
41
   9.3%
40
   9.1%
40
   9.2%
121
   9.2%
Serbia
34
   7.7%
34
   7.7%
34
   7.9%
102
   7.8%
Slovakia
2
   0.5%
1
   0.2%
2
   0.5%
5
   0.4%
South Africa
6
   1.4%
5
   1.1%
7
   1.6%
18
   1.4%
Spain
19
   4.3%
17
   3.9%
19
   4.4%
55
   4.2%
Ukraine
77
  17.5%
78
  17.8%
78
  18.0%
233
  17.7%
United Kingdom
6
   1.4%
6
   1.4%
4
   0.9%
16
   1.2%
United States
15
   3.4%
15
   3.4%
16
   3.7%
46
   3.5%
Type of Multiple Sclerosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
Relapsing-remitting multiple sclerosis
432
  98.0%
432
  98.4%
425
  98.2%
1289
  98.2%
Progressive-relapsing multiple sclerosis
8
   1.8%
7
   1.6%
8
   1.8%
23
   1.8%
Secondary progressive multiple sclerosis
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Age at MS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
28.9  (8.60) 29.3  (8.41) 29.2  (8.67) 29.1  (8.56)
Age at MS Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
31.6  (8.82) 32.0  (8.59) 32.1  (8.95) 31.9  (8.78)
Time Since MS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
6.36  (6.065) 6.23  (5.547) 6.92  (6.201) 6.50  (5.947)
Expanded Disability Status Scale (EDSS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
2.49  (1.158) 2.48  (1.166) 2.55  (1.145) 2.51  (1.156)
[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 from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is also scored. Based on scores in the 8 functional systems plus 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.
EDSS Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 441 participants 439 participants 433 participants 1313 participants
EDSS ≤ 3.5
375
  85.0%
374
  85.2%
371
  85.7%
1120
  85.3%
EDSS > 3.5
66
  15.0%
65
  14.8%
62
  14.3%
193
  14.7%
[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.
Number of Gadolinium-enhancing (GdE) Lesions   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 440 participants 439 participants 433 participants 1312 participants
1.8  (3.54) 1.8  (3.62) 1.6  (3.78) 1.7  (3.65)
[1]
Measure Description: A lesion appearing on magnetic resonance imagery (MRI), following injection of the chemical compound gadolinium, that reveals a breakdown in the blood-brain barrier. This breakdown of the blood-brain barrier indicates either a newly active lesion or the re-activation of an old one.
[2]
Measure Analysis Population Description: Participants with available MRI data
Number of T2 Lesions   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 440 participants 439 participants 432 participants 1311 participants
48.7  (32.62) 48.7  (36.27) 47.9  (32.37) 48.4  (33.78)
[1]
Measure Description: A T2-weighted MRI scan shows the number of old and new lesions in a specific part of the brain or spinal cord.
[2]
Measure Analysis Population Description: Participants with available MRI data
Normalized Brain Volume   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Cm³
Number Analyzed 439 participants 437 participants 432 participants 1308 participants
1449.581  (77.156) 1452.852  (71.978) 1441.949  (79.228) 1448.153  (76.250)
[1]
Measure Description: Measured using MRI
[2]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Adjusted Annualized Relapse Rate (ARR) at the End of Month 24
Hide Description

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 confirmed relapses divided by the total number of days in the study * 365.25.

ARR was based on a Poisson regression model, adjusted for region (Eastern Europe vs Rest of the World), age, and the Baseline number of gadolinium-enhancing lesions, and included the natural log transformation of time on study as an offset term.

Time Frame At the end of month 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included 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.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses/year
0.276
(0.234 to 0.324)
0.218
(0.183 to 0.259)
0.172
(0.142 to 0.208)
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, age, and Baseline 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 0.623
Confidence Interval (2-Sided) 95%
0.506 to 0.768
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 0.0167
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, age, and Baseline 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 0.791
Confidence Interval (2-Sided) 95%
0.652 to 0.958
Estimation Comments Rate Ratio = Ozanimod / IFN β-1a
2.Secondary Outcome
Title Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 24 Months
Hide Description

The adjusted mean 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 24 months. MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

The adjusted mean per scan over 24 months was based based on a negative binomial regression model using observed data, adjusted for region (Eastern Europe vs. Rest of the World), age at Baseline, and Baseline number of GdE lesions. The natural log transformation of the number of available MRI scans over 24 months is used as an offset term.

Time Frame 24 month treatment period; MRI scans were performed at Months 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all randomized participants who received at least 1 dose of study drug. Includes 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 IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 336 329 327
Least Squares Mean (95% Confidence Interval)
Unit of Measure: lesions/scan
3.183
(2.640 to 3.838)
2.092
(1.741 to 2.514)
1.835
(1.523 to 2.211)
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 control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Negative Binomial Regression Model
Comments Adjusted for region, age, and Baseline GdE lesions, and included the natural log transformation of available number of MRI scans as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.576
Confidence Interval (2-Sided) 95%
0.465 to 0.714
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 0.0001
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Negative binomial regression model
Comments Adjusted for region, age, and Baseline GdE lesions and included the natural log transformation of available number of MRI scans as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.657
Confidence Interval (2-Sided) 95%
0.531 to 0.813
Estimation Comments Rate Ratio = Ozanimod / IFN β-1a
3.Secondary Outcome
Title Adjusted Mean Number of Gadolinium Enhancing Brain Lesions at Month 24
Hide Description

MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

The number of gadolinium-enhancing (GdE) lesions at 24 months was analyzed based on observed data using a negative binomial regression model adjusted for region (Eastern Europe vs Rest of World), Baseline age, and Baseline number of GdE lesions, with natural log transformation of number of available MRI scans over 24 months as an offset term (1 scan for per participant).

Time Frame Month 24
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. Includes participants with non-missing GdE MRI results at Month 24.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 336 329 327
Least Squares Mean (95% Confidence Interval)
Unit of Measure: lesions
0.373
(0.256 to 0.543)
0.197
(0.131 to 0.296)
0.176
(0.116 to 0.266)
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 To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Negative Binomial Regression Model
Comments Adjusted for region, age, and Baseline GdE lesions with the natural log transformation of available MRI scans at Month 24 as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.471
Confidence Interval (2-Sided) 95%
0.306 to 0.725
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 0.0030
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Negative binomial regression model,
Comments Adjusted for region, age, and Baseline GdE lesions with the natural log transformation of available MRI scans at Month 24 as an offset term.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.528
Confidence Interval (2-Sided) 95%
0.346 to 0.805
Estimation Comments Rate ratio = Ozanimod / IFN β-1a
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 24-month treatment period
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 IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
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 0.8224
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Cox proportional hazards model
Comments Adjusted for region (Eastern Europe vs Rest of World) age at Baseline, and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.045
Confidence Interval (2-Sided) 95%
0.711 to 1.537
Estimation Comments Hazard ratio (Ozanimod / IFN β-1a) based on Cox proportional hazard model with factors for treatment group, adjusted for region, age at Baseline, and Baseline EDSS score.
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 0.2849
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Cox proportional hazards model
Comments Adjusted for region (Eastern Europe vs Rest of World), age at Baseline, and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.798
Confidence Interval (2-Sided) 95%
0.528 to 1.206
Estimation Comments Hazard ratio (Ozanimod / IFN β-1a) based on Cox proportional hazard model with factors for treatment group, adjusted for region, age at Baseline, and Baseline EDSS score.
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 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 24-month treatment period
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 IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
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 0.1353
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Cox proportional hazard model
Comments Adjusted for region (Eastern Europe vs Rest of World), age at Baseline, and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.435
Confidence Interval (2-Sided) 95%
0.893 to 2.305
Estimation Comments Hazard ratio (Ozanimod / IFN β-1a) based on Cox proportional hazard model with factors for treatment group, adjusted for region, age at Baseline, and Baseline EDSS score.
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 0.7154
Comments To control for type 1 error, the key secondary endpoints were tested in order in a sequential, closed hierarchical testing procedure. Each comparison was tested at the alpha = 0.05 level.
Method Cox proportional hazard model
Comments Adjusted for region (Eastern Europe vs Rest of World), age at Baseline, and Baseline EDSS score
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.098
Confidence Interval (2-Sided) 95%
0.664 to 1.815
Estimation Comments Hazard ratio (Ozanimod / IFN β-1a) based on Cox proportional hazard model with factors for treatment group, adjusted for region, age at Baseline, and Baseline EDSS score.
6.Secondary Outcome
Title Percentage of Participants Who Were Gadolinium Enhancing (GdE) Lesion-Free at Month 24
Hide Description

Participants were considered lesion free at Month 24 if they did not show evidence of GdE lesions at the Month 24 MRI scan.

MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

Time Frame Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received at least 1 dose of study drug; participants with missing data at Month 24 were considered non-responders.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
56.2
(51.6 to 60.9)
63.3
(58.8 to 67.8)
65.6
(61.1 to 70.1)
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 0.0047
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by region (Eastern Europe vs Rest of the World) and Baseline EDSS category
Method of Estimation Estimation Parameter Difference
Estimated Value 9.4
Confidence Interval (2-Sided) 95%
2.9 to 15.8
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 0.0320
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by region (Eastern Europe vs Rest of the World) and Baseline EDSS category
Method of Estimation Estimation Parameter Difference
Estimated Value 7.1
Confidence Interval (2-Sided) 95%
0.6 to 13.6
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Who Were New or Enlarging T2 Lesion-Free at Month 24
Hide Description MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Time Frame Month 24
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; Participants with missing data at Month 24 were considered non-responders.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.4
(14.8 to 22.0)
23.5
(19.5 to 27.4)
23.8
(19.8 to 27.8)
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 0.0466
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the Cochran-Mantel-Haenszel test stratified by region (Eastern Europe vs. rest of the world) and Baseline EDSS category
Method of Estimation Estimation Parameter Difference
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
0.0 to 10.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.0581
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Based on the Cochran-Mantel-Haenszel test stratified by region (Eastern Europe vs. rest of the world) and Baseline EDSS category
Method of Estimation Estimation Parameter Difference
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
-0.3 to 10.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Normalized Brain Volume to Month 24
Hide Description Brain volume (a measure of brain atrophy) was measured by brain MRI scans that were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Time Frame Baseline and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; last observation carried forward was used for participants with missing data at Month 24 (only post-baseline MRI scans were carried forward)
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 397 398 390
Mean (Standard Deviation)
Unit of Measure: percent change
-0.937  (0.944) -0.707  (0.746) -0.707  (0.878)
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 Based on the analysis of covariance model, adjusted for region (Eastern Europe vs. rest of the world), Baseline EDSS category, and brain volume at Baseline
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.244
Confidence Interval (2-Sided) 95%
0.125 to 0.363
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs. rest of the world), Baseline EDSS category, and brain volume at Baseline.
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 0.0002
Comments Based on the analysis of covariance model, adjusted for region (Eastern Europe vs. rest of the world), Baseline EDSS category, and brain volume at Baseline.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.224
Confidence Interval (2-Sided) 95%
0.106 to 0.342
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs. rest of the world), Baseline EDSS category, and brain volume at Baseline.
9.Secondary Outcome
Title Change From Baseline to Month 24 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 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population with available MSFC Z-scores
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 437 435 428
Mean (Standard Deviation)
Unit of Measure: Z-score
-0.052  (0.601) 0.036  (0.440) -0.010  (0.622)
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 0.2480
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and Baseline MSFC Z-score
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.043
Confidence Interval (2-Sided) 95%
-0.030 to 0.116
Estimation Comments Difference in means are based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and the Baseline MSFC Z-score.
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 0.0123
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and Baseline MSFC Z-score
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.093
Confidence Interval (2-Sided) 95%
0.020 to 0.165
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and the Baseline MSFC Z-score.
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 24
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. Missing data were imputed using a mixed-effects regression model.
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 441 439 433
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Health Composite Summary -1.526  (12.319) 0.609  (12.315) 0.209  (12.321)
Mental Health Composite Summary -1.831  (16.422) -1.182  (14.379) -1.517  (15.544)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments Analysis of Physical Health Composite Summary Score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0988
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and Baseline summary score
Method of Estimation Estimation Parameter Difference in means
Estimated Value 1.345
Confidence Interval (2-Sided) 95%
-0.252 to 2.943
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and Baseline summary score.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments Analysis of Physical Health Composite Summary Score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0228
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and Baseline summary score.
Method of Estimation Estimation Parameter Difference in means
Estimated Value 1.849
Confidence Interval (2-Sided) 95%
0.258 to 3.440
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and Baseline summary score.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 1 mg
Comments Analysis of Mental Health Composite Summary Score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6997
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and Baseline summary score
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.380
Confidence Interval (2-Sided) 95%
-1.553 to 2.313
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and Baseline summary score.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Ozanimod 0.5 mg
Comments Analysis of Mental Health Composite Summary Score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5501
Comments [Not Specified]
Method ANCOVA
Comments Based on the analysis of covariance model, adjusted for region, Baseline EDSS category, and the Baseline summary score
Method of Estimation Estimation Parameter Difference in means
Estimated Value 0.587
Confidence Interval (2-Sided) 95%
-1.339 to 2.513
Estimation Comments Difference in means based on the analysis of covariance model, adjusted for region (Eastern Europe vs Rest of the World), Baseline EDSS category, and Baseline summary score.
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), including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes.

The investigator assessed the severity of AEs as mild, moderate, or severe and the relationship of each AE to treatment as unrelated, unlikely, possible, probable, or related based on timing and other known factors such as clinical state, environment, or other therapies.

Time Frame From the first dose of study drug up to the first dose of the open-label extension study RPC01-3001, or up to 28 days after last dose for participants who did not continue into the open-label extension study; median duration of treatment was 24 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug, analyzed according to the highest dose of ozanimod treatment actually received, 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 IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 440 439 434
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
365
  83.0%
326
  74.3%
324
  74.7%
Any Moderate or Severe TEAE
235
  53.4%
169
  38.5%
170
  39.2%
Any Severe TEAE
19
   4.3%
19
   4.3%
15
   3.5%
Any Related TEAE
30
   6.8%
12
   2.7%
19
   4.4%
Any Serious TEAE
28
   6.4%
31
   7.1%
28
   6.5%
Any Related Serious TEAE
0
   0.0%
1
   0.2%
1
   0.2%
Any TEAE Leading to discontinuation of Study Drug
18
   4.1%
14
   3.2%
13
   3.0%
Any TEAE Leading to Study Withdrawal
20
   4.5%
13
   3.0%
13
   3.0%
Any Death on Study
0
   0.0%
1
   0.2%
0
   0.0%
12.Post-Hoc Outcome
Title Percent Change From Baseline in Normalized Brain Volume to Month 24 Based on Rank ANCOVA
Hide Description

Brain volume (a measure of brain atrophy) was measured by brain MRI scans that were read at a centralized MRI reading facility by a blinded reader.

Due to the non-normal distribution of the data for brain volume loss, the analyses for percent change from Baseline in normalized brain volume was repeated using rank-analysis of covariance (ANCOVA) and observed values.

Time Frame Baseline and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; participants with available data at Baseline and Month 24
Arm/Group Title Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months.
Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months.
Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
Overall Number of Participants Analyzed 279 274 271
Median (Full Range)
Unit of Measure: percent change
-0.940
(-5.33 to 1.44)
-0.710
(-5.21 to 1.36)
-0.690
(-5.65 to 0.85)
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 [Not Specified]
Method Rank ANCOVA
Comments Adjusted for region and Baseline EDSS category, with the dependent variable as the residual of the rank of brain volume at Baseline
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 <0.0001
Comments [Not Specified]
Method Rank ANCOVA
Comments Adjusted for region and Baseline EDSS category, with the dependent variable as the residual of the rank of brain volume at Baseline
Time Frame From first dose of study drug to 28 days following the last dose of study drug; median duration of treatment was 24 months in each treatment group.
Adverse Event Reporting Description The Safety Population included all participants who received at least 1 dose of study drug, analyzed according to the highest dose of ozanimod treatment actually received, 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 IFN β-1a 30 µg intramuscular injection weekly and matching placebo capsules (identical in physical appearance to ozanimod) orally daily for 24 months. Participants received ozanimod 0.5 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to Interferon) weekly for 24 months. Participants received ozanimod 1 mg oral capsules daily and an intramuscular placebo injection (identical in appearance to interferon) weekly for 24 months.
All-Cause Mortality
Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/440 (0.00%)   1/439 (0.23%)   0/434 (0.00%) 
Hide Serious Adverse Events
Interferon Beta-1a Ozanimod 0.5 mg Ozanimod 1 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/440 (6.36%)   31/439 (7.06%)   28/434 (6.45%) 
Cardiac disorders       
Acute Myocardial Infarction  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Atrial Fibrillation  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Sinus Tachycardia  1  0/440 (0.00%)  2/439 (0.46%)  0/434 (0.00%) 
Supraventricular Tachycardia  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Endocrine disorders       
Goitre  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Eye disorders       
Keratoconus  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Gastrointestinal disorders       
Abdominal Pain  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Abdominal Wall Haematoma  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Large Intestine Polyp  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Umbilical Hernia  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
General disorders       
Cyst  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Drowning  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Fatigue  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Pyrexia  1  1/440 (0.23%)  0/439 (0.00%)  1/434 (0.23%) 
Hepatobiliary disorders       
Cholecystitis Chronic  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Cholelithiasis  1  1/440 (0.23%)  1/439 (0.23%)  0/434 (0.00%) 
Hyperplastic Cholecystopathy  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Infections and infestations       
Acute Hepatitis B  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Appendicitis  1  2/440 (0.45%)  1/439 (0.23%)  2/434 (0.46%) 
Chronic Sinusitis  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Diverticulitis  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Gastroenteritis  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Pneumonia  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Pyelonephritis Acute  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Tonsillitis  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Injury, poisoning and procedural complications       
Ankle Fracture  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Carbon Monoxide Poisoning  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Clavicle Fracture  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Comminuted Fracture  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Concussion  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Craniocerebral Injury  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Intentional Overdose  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Jaw Fracture  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Joint Injury  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Ligament Sprain  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Lower Limb Fracture  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Lumbar Vertebral Fracture  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Traumatic Fracture  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Investigations       
Hepatic Enzyme Increased  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back Pain  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Intervertebral Disc Disorder  1  1/440 (0.23%)  0/439 (0.00%)  1/434 (0.23%) 
Intervertebral Disc Protrusion  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Osteitis  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Pseudarthrosis  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast Cancer  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Chronic Lymphocytic Leukaemia  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Invasive Breast Carcinoma  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Keratoacanthoma  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Malignant Melanoma In Situ  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Medulloblastoma  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Ovarian Fibroma  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Nervous system disorders       
Acoustic Neuritis  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Autonomic Nervous System Imbalance  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Central Nervous System Lesion  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Cerebral Haemorrhage  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Cerebral Infarction  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Cervical Radiculopathy  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Epilepsy  1  1/440 (0.23%)  1/439 (0.23%)  1/434 (0.23%) 
Generalised Tonic-Clonic Seizure  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Guillain-Barre Syndrome  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Headache  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Lumbar Radiculopathy  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Multiple Sclerosis Relapse  1  1/440 (0.23%)  1/439 (0.23%)  0/434 (0.00%) 
Neuralgia  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Sciatica  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Seizure  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Speech Disorder  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Syncope  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Foetal Growth Restriction  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Placental Polyp  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Vanishing Twin Syndrome  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Psychiatric disorders       
Suicide Attempt  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Renal and urinary disorders       
Calculus Urinary  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Chronic Kidney Disease  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Renal Colic  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Urethral Stenosis  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Reproductive system and breast disorders       
Breast Cyst  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Cervical Polyp  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Dysfunctional Uterine Bleeding  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Endometriosis  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Metrorrhagia  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Ovarian Cyst  1  0/440 (0.00%)  0/439 (0.00%)  2/434 (0.46%) 
Uterine Polyp  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary Embolism  1  0/440 (0.00%)  0/439 (0.00%)  1/434 (0.23%) 
Skin and subcutaneous tissue disorders       
Skin Ulcer  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Urticaria  1  0/440 (0.00%)  1/439 (0.23%)  0/434 (0.00%) 
Vascular disorders       
Hypertension  1  1/440 (0.23%)  0/439 (0.00%)  0/434 (0.00%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
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   275/440 (62.50%)   185/439 (42.14%)   199/434 (45.85%) 
General disorders       
Influenza Like Illness  1  215/440 (48.86%)  26/439 (5.92%)  27/434 (6.22%) 
Pyrexia  1  27/440 (6.14%)  12/439 (2.73%)  10/434 (2.30%) 
Infections and infestations       
Nasopharyngitis  1  48/440 (10.91%)  59/439 (13.44%)  68/434 (15.67%) 
Pharyngitis  1  15/440 (3.41%)  24/439 (5.47%)  17/434 (3.92%) 
Upper Respiratory Tract Infection  1  37/440 (8.41%)  36/439 (8.20%)  34/434 (7.83%) 
Urinary Tract Infection  1  17/440 (3.86%)  22/439 (5.01%)  19/434 (4.38%) 
Investigations       
Alanine Aminotransferase Increased  1  20/440 (4.55%)  29/439 (6.61%)  26/434 (5.99%) 
Gamma-Glutamyltransferase Increased  1  9/440 (2.05%)  16/439 (3.64%)  25/434 (5.76%) 
Nervous system disorders       
Headache  1  53/440 (12.05%)  55/439 (12.53%)  44/434 (10.14%) 
Vascular disorders       
Hypertension  1  14/440 (3.18%)  20/439 (4.56%)  24/434 (5.53%) 
Orthostatic Hypotension  1  27/440 (6.14%)  27/439 (6.15%)  30/434 (6.91%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
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. Investigator must delete confidential information before submission.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please email:
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02047734    
Other Study ID Numbers: RPC01-201-PartB
2012-002714-40 ( EudraCT Number )
First Submitted: January 26, 2014
First Posted: January 28, 2014
Results First Submitted: January 25, 2021
Results First Posted: February 11, 2021
Last Update Posted: February 11, 2021