Trial Outcomes & Findings for Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants (NCT NCT02342704)
NCT ID: NCT02342704
Last Updated: 2017-06-09
Results Overview
TERMINATED
PHASE4
111 participants
Up to Week 52
2017-06-09
Participant Flow
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.
Participant milestones
| Measure |
Natalizumab
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Overall Study
STARTED
|
54
|
54
|
|
Overall Study
COMPLETED
|
1
|
3
|
|
Overall Study
NOT COMPLETED
|
53
|
51
|
Reasons for withdrawal
| Measure |
Natalizumab
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
3
|
|
Overall Study
Sponsor Termination
|
49
|
43
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Adverse Event
|
1
|
3
|
Baseline Characteristics
Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
Baseline characteristics by cohort
| Measure |
Natalizumab
n=54 Participants
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=54 Participants
Open-label fingolimod 0.5 mg once daily orally
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.19 years
STANDARD_DEVIATION 8.811 • n=5 Participants
|
34.87 years
STANDARD_DEVIATION 8.731 • n=7 Participants
|
36.53 years
STANDARD_DEVIATION 8.887 • n=5 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 12, Week 24Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment.
Outcome measures
| Measure |
Natalizumab
n=47 Participants
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=45 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Cumulative Number of New T1-Gd+ Lesions
From Baseline to Week 4
|
0.62 lesions
Standard Deviation 1.512
|
1.69 lesions
Standard Deviation 4.122
|
|
Cumulative Number of New T1-Gd+ Lesions
From Baseline to Week 12
|
0.68 lesions
Standard Deviation 1.695
|
2.27 lesions
Standard Deviation 4.499
|
|
Cumulative Number of New T1-Gd+ Lesions
From Baseline to Week 24
|
0.72 lesions
Standard Deviation 1.69
|
2.6 lesions
Standard Deviation 4.745
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
As assessed by magnetic resonance imaging (MRI).
Outcome measures
| Measure |
Natalizumab
n=15 Participants
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=16 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
T1 Lesion Volume Change
|
0.5 percentage change
Standard Deviation 31.235
|
1.81 percentage change
Standard Deviation 19.703
|
|
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
T2 Lesion Volume Change
|
0.08 percentage change
Standard Deviation 4.399
|
3.32 percentage change
Standard Deviation 5.036
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
As assessed by MRI.
Outcome measures
| Measure |
Natalizumab
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=1 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
T1 Lesion Volume Change
|
—
|
-15.31 percentage change
Standard Deviation NA
only 1 participant had an assessment
|
|
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
T2 Lesion Volume Change
|
—
|
5.6 percentage change
Standard Deviation NA
only 1 participant had an assessment
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had an assessment.
Outcome measures
| Measure |
Natalizumab
n=15 Participants
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=16 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Cumulative Number of New or Enlarging T2 Lesions
|
1.33 lesions
Standard Deviation 2.469
|
1.94 lesions
Standard Deviation 2.205
|
SECONDARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
Natalizumab
n=14 Participants
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=17 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
|
3.79 units on a scale
Standard Deviation 8.684
|
3.24 units on a scale
Standard Deviation 4.63
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
Natalizumab
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=9 Participants
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Change From Baseline in SDMT at Week 52
|
—
|
2.11 units on a scale
Standard Deviation 8.492
|
Adverse Events
Natalizumab
Fingolimod
Serious adverse events
| Measure |
Natalizumab
n=54 participants at risk
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=54 participants at risk
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Cardiac disorders
Atrioventricular block second degree
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Migraine with aura
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
Other adverse events
| Measure |
Natalizumab
n=54 participants at risk
Open-label natalizumab 300 mg IV every 4 weeks
|
Fingolimod
n=54 participants at risk
Open-label fingolimod 0.5 mg once daily orally
|
|---|---|---|
|
Nervous system disorders
Headache
|
11.1%
6/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
7.4%
4/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Multiple sclerosis relapse
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
14.8%
8/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Migraine
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
9.3%
5/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Urinary tract infection
|
3.7%
2/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
9.3%
5/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Anxiety
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
1.9%
1/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
|
General disorders
Fatigue
|
5.6%
3/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
0.00%
0/54 • Up to 64 weeks.
Treatment-emergent adverse events are presented.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER