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Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants (REVEAL)

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ClinicalTrials.gov Identifier: NCT02342704
Recruitment Status : Terminated (Business Decision)
First Posted : January 21, 2015
Results First Posted : June 9, 2017
Last Update Posted : June 9, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: natalizumab
Drug: fingolimod
Enrollment 111
Recruitment Details  
Pre-assignment Details A total of 128 participants were screened, 111 participants were enrolled in the study. Three participants were not randomized and did not receive any dose of study drug.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description Open-label natalizumab 300 mg IV every 4 weeks Open-label fingolimod 0.5 mg once daily orally
Period Title: Overall Study
Started 54 [1] 54 [1]
Completed 1 3
Not Completed 53 51
Reason Not Completed
Physician Decision             0             3
Sponsor Termination             49             43
Other             0             1
Withdrawal by Subject             1             0
Lost to Follow-up             2             1
Adverse Event             1             3
[1]
Safety Population: randomized participants who received at least 1 dose of study treatment.
Arm/Group Title Natalizumab Fingolimod Total
Hide Arm/Group Description Open-label natalizumab 300 mg IV every 4 weeks Open-label fingolimod 0.5 mg once daily orally Total of all reporting groups
Overall Number of Baseline Participants 54 54 108
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants 54 participants 108 participants
38.19  (8.811) 34.87  (8.731) 36.53  (8.887)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 54 participants 108 participants
Female
37
  68.5%
38
  70.4%
75
  69.4%
Male
17
  31.5%
16
  29.6%
33
  30.6%
1.Primary Outcome
Title Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions
Hide Description [Not Specified]
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Cumulative Number of New T1-Gd+ Lesions
Hide Description [Not Specified]
Time Frame Baseline, Week 4, Week 12, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 47 45
Mean (Standard Deviation)
Unit of Measure: lesions
From Baseline to Week 4 0.62  (1.512) 1.69  (4.122)
From Baseline to Week 12 0.68  (1.695) 2.27  (4.499)
From Baseline to Week 24 0.72  (1.69) 2.6  (4.745)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1260
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3525
Comments [Not Specified]
Method negative binomial regression
Comments p-value is based on negative binomial regression model, adjusted for baseline GD lesion count
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0127
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0299
Comments [Not Specified]
Method negative binomial regression
Comments p-value is based on negative binomial regression model, adjusted for baseline GD lesion count
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0076
Comments [Not Specified]
Method negative binomial regression
Comments p-value is based on negative binomial regression model, adjusted for baseline GD lesion count
3.Secondary Outcome
Title Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
Hide Description As assessed by magnetic resonance imaging (MRI).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 15 16
Mean (Standard Deviation)
Unit of Measure: percentage change
T1 Lesion Volume Change 0.5  (31.235) 1.81  (19.703)
T2 Lesion Volume Change 0.08  (4.399) 3.32  (5.036)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments T1 Lesion Volume Change
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5318
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments T2 Lesion Volume Change
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0528
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
4.Secondary Outcome
Title Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
Hide Description As assessed by MRI.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 1
Mean (Standard Deviation)
Unit of Measure: percentage change
T1 Lesion Volume Change -15.31 [1]   (NA)
T2 Lesion Volume Change 5.6 [1]   (NA)
[1]
only 1 participant had an assessment
5.Secondary Outcome
Title Cumulative Number of New or Enlarging T2 Lesions
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 15 16
Mean (Standard Deviation)
Unit of Measure: lesions
1.33  (2.469) 1.94  (2.205)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Fingolimod
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2632
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments p-value is based on Wilcoxon rank-sum test between the 2 treatment groups
6.Secondary Outcome
Title Proportion of Participants With No Evidence of Disease Activity (NEDA)
Hide Description NEDA was defined as all of the following: no relapses; no 12-week confirmed disability progression based on Expanded Disability Status Scale (EDSS; defined as an increase of 1.0 or more on the EDSS from baseline of 1.0 or more, or an increase of 1.5 or more from a baseline score of 0) that was sustained for 12 weeks; no new T1-Gd+ lesions on brain MRI. No new or enlarging T2-hyperintense lesions.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Time to First Relapse
Hide Description A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Cumulative Risk of Relapse
Hide Description A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Time to Complete Recovery From First Relapse
Hide Description 12-week confirmed complete EDSS recovery from first on-treatment relapse is defined as an EDSS score that is equal to or lower than the last pre-relapse EDSS score and sustained for at least 12 weeks.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
Hide Description The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had both baseline and post-baseline values.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 14 17
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.79  (8.684) 3.24  (4.63)
11.Secondary Outcome
Title Change From Baseline in SDMT at Week 52
Hide Description The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had both baseline and post-baseline values.
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description:
Open-label natalizumab 300 mg IV every 4 weeks
Open-label fingolimod 0.5 mg once daily orally
Overall Number of Participants Analyzed 0 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.11  (8.492)
Time Frame Up to 64 weeks.
Adverse Event Reporting Description Treatment-emergent adverse events are presented.
 
Arm/Group Title Natalizumab Fingolimod
Hide Arm/Group Description Open-label natalizumab 300 mg IV every 4 weeks Open-label fingolimod 0.5 mg once daily orally
All-Cause Mortality
Natalizumab Fingolimod
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Natalizumab Fingolimod
Affected / at Risk (%) Affected / at Risk (%)
Total   0/54 (0.00%)   2/54 (3.70%) 
Cardiac disorders     
Atrioventricular block second degree † 1  0/54 (0.00%)  1/54 (1.85%) 
Nervous system disorders     
Migraine with aura † 1  0/54 (0.00%)  1/54 (1.85%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Natalizumab Fingolimod
Affected / at Risk (%) Affected / at Risk (%)
Total   14/54 (25.93%)   23/54 (42.59%) 
General disorders     
Fatigue † 1  3/54 (5.56%)  0/54 (0.00%) 
Infections and infestations     
Upper respiratory tract infection † 1  1/54 (1.85%)  5/54 (9.26%) 
Urinary tract infection † 1  2/54 (3.70%)  3/54 (5.56%) 
Investigations     
Lymphocyte count decreased † 1  0/54 (0.00%)  5/54 (9.26%) 
Alanine aminotransferase increased † 1  0/54 (0.00%)  3/54 (5.56%) 
Nervous system disorders     
Headache † 1  6/54 (11.11%)  4/54 (7.41%) 
Multiple sclerosis relapse † 1  1/54 (1.85%)  8/54 (14.81%) 
Hypoaesthesia † 1  0/54 (0.00%)  3/54 (5.56%) 
Migraine † 1  0/54 (0.00%)  3/54 (5.56%) 
Psychiatric disorders     
Anxiety † 1  1/54 (1.85%)  3/54 (5.56%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain † 1  3/54 (5.56%)  1/54 (1.85%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
[Not Specified]
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.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Biogen Study Medical Director
Organization: Biogen
EMail: clinicaltrials@biogen.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02342704    
Other Study ID Numbers: 101MS408
2013-004622-29 ( EudraCT Number )
First Submitted: January 15, 2015
First Posted: January 21, 2015
Results First Submitted: May 17, 2017
Results First Posted: June 9, 2017
Last Update Posted: June 9, 2017