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Efficacy and Safety Study of Ozanimod (RPC1063) in Relapsing Multiple Sclerosis Patients (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: NCT01628393
Recruitment Status : Completed
First Posted : June 26, 2012
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: Placebo
Enrollment 258
Recruitment Details

The study was conducted at 55 study centers in 13 countries including the United States, Europe and Russia. Participants with multiple sclerosis (MS) were recruited between September 2012 and October 2013.

The study consisted of a 24-week placebo-controlled treatment period and an optional 96-week blinded extension period.

Pre-assignment Details Participants were randomly assigned in a 1:1:1 ratio to receive one of two daily doses of ozanimod (0.5 mg or 1 mg) or matching placebo for 24 weeks. Those who completed 24 weeks could enter a blinded extension phase and continue on their assigned doses of ozanimod, whereas those assigned to placebo were re-randomized in a 1:1 ratio to ozanimod 0.5 mg or 1 mg. In both periods the randomization was stratified by country.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg Placebo / Ozanimod 0.5 mg Placebo / Ozanimod 1 mg
Hide Arm/Group Description Participants received placebo capsules by mouth (PO) daily during the 24-week placebo-controlled treatment period. Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension phase and continued to receive ozanimod 0.5 mg capsules PO daily for an additional 96 weeks of treatment. Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension phase and continued to receive ozanimod 1 mg capsules PO daily for an additional 96 weeks of treatment. Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 0.5 mg PO daily during the blinded extension period for 96 weeks. Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 1 mg PO daily during the blinded extension period for 96 weeks.
Period Title: Placebo-controlled Treatment Period
Started 88 87 83 0 0
Completed 85 85 82 0 0
Not Completed 3 2 1 0 0
Reason Not Completed
Lost to Follow-up             1             0             0             0             0
Protocol Violation             0             1             0             0             0
Withdrawal by Subject             2             1             1             0             0
Period Title: Blinded Active Extension Period
Started [1] 0 85 81 41 42
Completed 0 75 75 37 36
Not Completed 0 10 6 4 6
Reason Not Completed
Adverse Event             0             1             0             2             2
Lack of Efficacy             0             0             2             0             2
Physician Decision             0             3             0             1             0
Protocol Violation             0             0             2             1             0
Withdrawal by Subject             0             6             2             0             2
[1]
Three participants who completed the placebo-controlled treatment period declined to enter the blinded extension period.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg Total
Hide Arm/Group Description Participants received placebo capsules by mouth (PO) daily during the 24-week placebo-controlled treatment period. Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period. Total of all reporting groups
Overall Number of Baseline Participants 88 87 83 258
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population is defined as 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 88 participants 87 participants 83 participants 258 participants
39.0  (8.67) 38.1  (9.17) 38.4  (9.82) 38.5  (9.19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 87 participants 83 participants 258 participants
Female
62
  70.5%
60
  69.0%
59
  71.1%
181
  70.2%
Male
26
  29.5%
27
  31.0%
24
  28.9%
77
  29.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 87 participants 83 participants 258 participants
White
87
  98.9%
84
  96.6%
83
 100.0%
254
  98.4%
Black
1
   1.1%
2
   2.3%
0
   0.0%
3
   1.2%
Asian
0
   0.0%
1
   1.1%
0
   0.0%
1
   0.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 87 participants 83 participants 258 participants
North America
4
   4.5%
4
   4.6%
4
   4.8%
12
   4.7%
Western Europe
6
   6.8%
4
   4.6%
3
   3.6%
13
   5.0%
Eastern Europe
78
  88.6%
79
  90.8%
76
  91.6%
233
  90.3%
Country of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 87 participants 83 participants 258 participants
Poland
44
  50.0%
44
  50.6%
44
  53.0%
132
  51.2%
Serbia
12
  13.6%
12
  13.8%
13
  15.7%
37
  14.3%
Ukraine
9
  10.2%
10
  11.5%
9
  10.8%
28
  10.9%
Russia
6
   6.8%
7
   8.0%
6
   7.2%
19
   7.4%
United States
4
   4.5%
4
   4.6%
4
   4.8%
12
   4.7%
Romania
2
   2.3%
2
   2.3%
2
   2.4%
6
   2.3%
Georgia
2
   2.3%
2
   2.3%
1
   1.2%
5
   1.9%
Bulgaria
2
   2.3%
1
   1.1%
1
   1.2%
4
   1.6%
Greece
1
   1.1%
1
   1.1%
2
   2.4%
4
   1.6%
Spain
2
   2.3%
1
   1.1%
1
   1.2%
4
   1.6%
Italy
2
   2.3%
1
   1.1%
0
   0.0%
3
   1.2%
Belgium
1
   1.1%
1
   1.1%
0
   0.0%
2
   0.8%
Hungary
1
   1.1%
1
   1.1%
0
   0.0%
2
   0.8%
Age at Multiple Sclerosis Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 87 participants 83 participants 258 participants
33.9  (8.30) 34.8  (10.01) 34.4  (9.51) 34.4  (9.27)
Time Since Multiple Sclerosis Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 87 participants 83 participants 258 participants
4.6  (5.12) 2.8  (4.98) 3.6  (4.43) 3.7  (4.90)
Expanded Disability Status Scale (EDSS) Score at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 88 participants 87 participants 83 participants 258 participants
2.85  (1.273) 2.94  (1.287) 2.86  (1.213) 2.88  (1.255)
[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.
Time Since MS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 87 participants 83 participants 258 participants
8.1  (6.97) 6.0  (6.41) 6.2  (5.79) 6.8  (6.47)
Number of Relapses Within the Last 12 months Prior to Screening  
Mean (Standard Deviation)
Unit of measure:  Relapses
Number Analyzed 88 participants 87 participants 83 participants 258 participants
1.3  (0.64) 1.5  (1.18) 1.3  (0.73) 1.4  (0.88)
Number of Relapses Within the Last 24 months Prior to Screening  
Mean (Standard Deviation)
Unit of measure:  Relapses
Number Analyzed 88 participants 87 participants 83 participants 258 participants
1.8  (1.01) 2.0  (1.79) 1.9  (1.05) 1.9  (1.33)
Number of Gadolinium Enhancing (GdE) Lesions   [1] 
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 88 participants 87 participants 83 participants 258 participants
1.4  (3.36) 0.9  (1.42) 1.3  (2.75) 1.2  (2.64)
[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.
1.Primary Outcome
Title Total Number of Gadolinium-Enhancing (GdE) Lesions Assessed on Brain Magnetic Resonance Imaging (MRI) From Week 12 to Week 24
Hide Description The cumulative number of total GdE lesions on MRI from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Time Frame From Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description

The ITT population is defined as all randomized participants who received at least 1 dose of study drug.

Missing data were imputed using the last valid non-missing, post-baseline observation which was carried forward if the participant was only missing 1 or 2 consecutive post-baseline scans. If there were no post-baseline data or the participant was missing > 2 consecutive scans, the mean number of lesions from participants in the same treatment group and visit was used as the imputed value.

Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received placebo capsules PO daily during the 24-week placebo-controlled period.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Overall Number of Participants Analyzed 88 87 83
Mean (Standard Deviation)
Unit of Measure: lesions
11.1  (29.87) 1.9  (4.77) 1.5  (3.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 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 = 0.04944 level of significance to keep the overall level of significance at 0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 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 account for multiple comparisons, each of the 2 treatment comparisons was tested at the alpha = 0.04944 level of significance to keep the overall level of significance at 0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
2.Secondary Outcome
Title The Number of Gadolinium-Enhancing Lesions on Brain MRI Scan at Week 24
Hide Description MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is defined as all randomized participants who received at least 1 dose of study drug. Missing GdE data values were imputed using the mean number of lesions from participants in the same treatment group at the same visit.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received placebo capsules PO daily during the 24-week placebo-controlled period.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Overall Number of Participants Analyzed 88 87 83
Mean (Standard Deviation)
Unit of Measure: lesions
3.2  (9.81) 0.4  (1.27) 0.2  (0.59)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 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 Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 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 Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
3.Secondary Outcome
Title The Total Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions From Week 12 to Week 24
Hide Description

The cumulative number of new or enlarging hyperintense T2-weighted brain MRI lesions from Week 12 to Week 24.

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

Time Frame Week 12 to Week 24; MRI was performed at Weeks 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is defined as all randomized participants who received at least 1 dose of study drug. Missing new or enlarging T2 data values were imputed using the mean from participants of the same treatment group at the same visit.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received placebo capsules PO daily during the 24-week placebo-controlled period.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Overall Number of Participants Analyzed 88 87 83
Mean (Standard Deviation)
Unit of Measure: lesions
9.0  (20.87) 1.4  (3.21) 0.8  (1.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 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 Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 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 Wilcoxon (Mann-Whitney)
Comments Wilcoxon-Mann-Whitney test stratified by absence or presence of gadolinium-enhancing lesions at Baseline.
4.Secondary Outcome
Title Adjusted Annualized Relapse Rate (ARR) at Week 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.

ARR was based on a Poisson regression model, adjusted for region, relapses within 24 months before the study, and presence of gadolinium-enhancing lesions at Baseline.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is defined as all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received placebo capsules PO daily during the 24-week placebo-controlled period.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Overall Number of Participants Analyzed 88 87 83
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses/year
0.50
(0.22 to 1.15)
0.35
(0.15 to 0.82)
0.24
(0.09 to 0.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanimod 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0531
Comments [Not Specified]
Method Poisson regression model
Comments Adjusted for region, the number of relapses within 24 months prior to the study, and the absence or presence of GdE lesions at Baseline.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.22 to 1.01
Estimation Comments Rate ratio = Ozanimod / Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ozanimod 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2714
Comments [Not Specified]
Method Poisson regression model
Comments Adjusted for region, the number of relapses within 24 months prior to the study, and the absence or presence of GdE lesions at Baseline.
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.36 to 1.34
Estimation Comments Rate ratio = Ozanimod / Placebo
5.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Treatment Period
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 first dose of study drug up to Week 24, or up to 28 days after the last dose for participants who did not enter the extension period.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least one dose of study drug.
Arm/Group Title Placebo Ozanimod 0.5 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants received placebo capsules PO daily during the 24-week placebo-controlled period.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period.
Overall Number of Participants Analyzed 88 87 83
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
52
  59.1%
57
  65.5%
47
  56.6%
Any moderate or severe TEAE
23
  26.1%
23
  26.4%
13
  15.7%
Any severe TEAE
1
   1.1%
2
   2.3%
1
   1.2%
Any TEAE related to study drug
1
   1.1%
1
   1.1%
0
   0.0%
Any serious TEAE
0
   0.0%
3
   3.4%
0
   0.0%
Any serious TEAE related to study drug
0
   0.0%
0
   0.0%
0
   0.0%
Any TEAE leading to discontinuation of study drug
0
   0.0%
0
   0.0%
0
   0.0%
Any death related to study drug
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAE) During Ozanimod Exposure
Hide Description

AEs are reported from the start of the placebo-controlled period for participants originally assigned to ozanimod and from the start of the extension period for participants who switched to ozanimod after Week 24.

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 based on timing and other known factors such as clinical state, environment, or other therapies.

Time Frame From the first dose of ozanimod, either in the placebo-controlled or the blinded extension period, up to 4 weeks after the last dose; mean duration of exposure was 25.4, 30.9, 24.6, and 32.3 months in each treatment group respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least one dose of study drug in the blinded extension phase
Arm/Group Title Placebo / Ozanimod 0.5 mg Ozanimod 0.5 mg Placebo / Ozanimod 1 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 0.5 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 0.5 mg capsules PO daily for an additional 96 weeks.
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 1 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 1 mg capsules PO daily for an additional 96 weeks.
Overall Number of Participants Analyzed 41 85 42 81
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
26
  63.4%
73
  85.9%
32
  76.2%
61
  75.3%
Any moderate or severe TEAE
17
  41.5%
42
  49.4%
18
  42.9%
35
  43.2%
Any severe TEAE
2
   4.9%
4
   4.7%
1
   2.4%
2
   2.5%
Any TEAE related to study drug
2
   4.9%
3
   3.5%
1
   2.4%
3
   3.7%
Any serious TEAE
2
   4.9%
10
  11.8%
3
   7.1%
6
   7.4%
Any serious TEAE related to study drug
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any TEAE leading to discontinuation of study drug
2
   4.9%
1
   1.2%
1
   2.4%
0
   0.0%
Any death related to study drug
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Post-Hoc Outcome
Title Number of Gadolinium-Enhancing (GdE) Lesions During the Extension Period
Hide Description MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.
Time Frame Weeks 24, 48, 72, and 120
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who entered the blinded extension period, received at least 1 dose of study drug, and had any post-baseline assessment in the blinded extension period. Includes participants with non-missing MRI results at each time point.
Arm/Group Title Placebo / Ozanimod 0.5 mg Ozanimod 0.5 mg Placebo / Ozanimod 1 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 0.5 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 0.5 mg capsules PO daily for an additional 96 weeks.
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 1 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 1 mg capsules PO daily for an additional 96 weeks.
Overall Number of Participants Analyzed 41 85 42 81
Mean (Standard Deviation)
Unit of Measure: lesions
Week 24 (start of extension period) Number Analyzed 41 participants 85 participants 42 participants 81 participants
4.5  (13.02) 0.4  (1.28) 1.9  (5.93) 0.2  (0.60)
Week 48 Number Analyzed 38 participants 80 participants 40 participants 79 participants
0.6  (2.63) 0.4  (1.30) 0.4  (1.35) 0.2  (0.56)
Week 72 Number Analyzed 38 participants 76 participants 37 participants 79 participants
0.4  (1.95) 0.4  (1.41) 0.1  (0.28) 0.2  (0.56)
Week 120 Number Analyzed 37 participants 72 participants 36 participants 74 participants
0.1  (0.46) 0.4  (1.49) 0.1  (0.37) 0.2  (0.51)
8.Post-Hoc Outcome
Title Total Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions In the Extension Period
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The cumulative number of new or enlarging hyperintense T2-weighted brain MRI lesions from Week 12 to Week 24 in the placebo controlled period (reference) and during the first and second years of the extension period.

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

Time Frame Weeks 12 to 24 of the placebo-controlled period and Week 24 to 72 (first year) and Week 72 - 120 (second year) in the extension period
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Hide Analysis Population Description
Participants who entered the blinded extension period, received at least 1 dose of study drug, and had any post-baseline assessment in the blinded extension period. Includes participants with non-missing MRI results in each time period.
Arm/Group Title Placebo / Ozanimod 0.5 mg Ozanimod 0.5 mg Placebo / Ozanimod 1 mg Ozanimod 1 mg
Hide Arm/Group Description:
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 0.5 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 0.5 mg capsules PO daily for an additional 96 weeks.
Participants initially randomized to placebo during the 24-week placebo controlled treatment period were re-randomized to receive ozanimod 1 mg capsules PO daily during the blinded extension period for 96 weeks.
Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled treatment period. Participants were given the option to enter into a blinded extension period and continued to receive ozanimod 1 mg capsules PO daily for an additional 96 weeks.
Overall Number of Participants Analyzed 41 85 42 81
Mean (Standard Error)
Unit of Measure: lesions
Week 12 to 24 Number Analyzed 41 participants 85 participants 42 participants 81 participants
10.8  (3.58) 1.4  (0.35) 7.3  (3.07) 0.9  (0.21)
Week 24 to 72 Number Analyzed 38 participants 76 participants 37 participants 79 participants
4.3  (1.99) 2.8  (0.72) 1.5  (0.39) 1.9  (0.84)
Week 72 to 120 Number Analyzed 37 participants 71 participants 36 participants 74 participants
3.2  (1.31) 2.3  (0.61) 1.9  (0.48) 0.7  (0.16)
Time Frame Placebo-controlled period: From first dose of study drug up to Week 24, or up to 28 days after the last dose for participants who did not enter the extension period. Extension period: From the first dose of ozanimod in the blinded extension period, up to 4 weeks after the last dose; up to 96 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo-Controlled Period: Placebo Placebo-Controlled Period: Ozanimod 0.5 mg Placebo-Controlled Period: Ozanimod 1.0 mg Extension Period: Ozanimod 0.5 mg Extension Period: Ozanimod 1.0 mg
Hide Arm/Group Description Participants received placebo capsules PO daily during the 24-week placebo-controlled period. Participants received ozanimod 0.5 mg capsules PO daily during the 24-week placebo-controlled period. Participants received ozanimod 1 mg capsules PO daily during the 24-week placebo-controlled period. Participants received ozanimod 0.5 mg capsules PO daily during the blinded extension period (Weeks 25 to 120). Participants received ozanimod 1 mg capsules PO daily during the blinded extension period (Weeks 25 to 120).
All-Cause Mortality
Placebo-Controlled Period: Placebo Placebo-Controlled Period: Ozanimod 0.5 mg Placebo-Controlled Period: Ozanimod 1.0 mg Extension Period: Ozanimod 0.5 mg Extension Period: Ozanimod 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/88 (0.00%)   0/87 (0.00%)   0/83 (0.00%)   0/126 (0.00%)   0/123 (0.00%) 
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Placebo-Controlled Period: Placebo Placebo-Controlled Period: Ozanimod 0.5 mg Placebo-Controlled Period: Ozanimod 1.0 mg Extension Period: Ozanimod 0.5 mg Extension Period: Ozanimod 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/88 (0.00%)   3/87 (3.45%)   0/83 (0.00%)   10/126 (7.94%)   9/123 (7.32%) 
Blood and lymphatic system disorders           
Pancytopenia  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Cardiac disorders           
Acute Myocardial Infarction  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Gastrointestinal disorders           
Irritable Bowel Syndrome  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Hepatobiliary disorders           
Hepatitis  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Infections and infestations           
Proctitis Infectious  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Injury, poisoning and procedural complications           
Clavicle Fracture  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Concussion  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Injury  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Lower Limb Fracture  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Musculoskeletal and connective tissue disorders           
Rheumatoid Arthritis  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Nervous system disorders           
Cauda Equina Syndrome  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Headache  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Intracranial Aneurysm  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Optic Neuritis  1  0/88 (0.00%)  1/87 (1.15%)  0/83 (0.00%)  0/126 (0.00%)  0/123 (0.00%) 
Psychiatric disorders           
Depression  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Somatoform Disorder  1  0/88 (0.00%)  1/87 (1.15%)  0/83 (0.00%)  0/126 (0.00%)  0/123 (0.00%) 
Renal and urinary disorders           
Urethral Stenosis  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Reproductive system and breast disorders           
Menometrorrhagia  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Ovarian Cyst  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Uterine Cervical Squamous Metaplasia  1  0/88 (0.00%)  1/87 (1.15%)  0/83 (0.00%)  0/126 (0.00%)  0/123 (0.00%) 
Uterine Haemorrhage  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Skin and subcutaneous tissue disorders           
Stasis Dermatitis  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  0/126 (0.00%)  1/123 (0.81%) 
Urticaria  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (0.00%) 
Vascular disorders           
Hypertension  1  0/88 (0.00%)  0/87 (0.00%)  0/83 (0.00%)  1/126 (0.79%)  0/123 (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%
Placebo-Controlled Period: Placebo Placebo-Controlled Period: Ozanimod 0.5 mg Placebo-Controlled Period: Ozanimod 1.0 mg Extension Period: Ozanimod 0.5 mg Extension Period: Ozanimod 1.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/88 (27.27%)   24/87 (27.59%)   10/83 (12.05%)   52/126 (41.27%)   43/123 (34.96%) 
Infections and infestations           
Nasopharyngitis  1  12/88 (13.64%)  11/87 (12.64%)  5/83 (6.02%)  17/126 (13.49%)  17/123 (13.82%) 
Upper Respiratory Tract Infection  1  3/88 (3.41%)  4/87 (4.60%)  3/83 (3.61%)  20/126 (15.87%)  11/123 (8.94%) 
Urinary Tract Infection  1  2/88 (2.27%)  6/87 (6.90%)  2/83 (2.41%)  7/126 (5.56%)  4/123 (3.25%) 
Investigations           
Alanine Aminotransferase Increased  1  0/88 (0.00%)  3/87 (3.45%)  4/83 (4.82%)  10/126 (7.94%)  12/123 (9.76%) 
Gamma-Glutamyltransferase Increased  1  0/88 (0.00%)  2/87 (2.30%)  5/83 (6.02%)  11/126 (8.73%)  8/123 (6.50%) 
Musculoskeletal and connective tissue disorders           
Back Pain  1  9/88 (10.23%)  5/87 (5.75%)  2/83 (2.41%)  5/126 (3.97%)  7/123 (5.69%) 
Nervous system disorders           
Headache  1  8/88 (9.09%)  5/87 (5.75%)  3/83 (3.61%)  7/126 (5.56%)  9/123 (7.32%) 
Vascular disorders           
Hypertension  1  1/88 (1.14%)  1/87 (1.15%)  2/83 (2.41%)  8/126 (6.35%)  2/123 (1.63%) 
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.
The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (30) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.
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
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01628393    
Other Study ID Numbers: RPC01-201-PartA
2012-002714-40 ( EudraCT Number )
First Submitted: June 22, 2012
First Posted: June 26, 2012
Results First Submitted: January 25, 2021
Results First Posted: February 11, 2021
Last Update Posted: February 11, 2021