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

• Sponsor: Biogen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02342704
• Collaborator: (none)
• Enrollment: 111
• Locations: 42
• Arms: 2
• Actual Duration (Months): 17.6
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the effect of natalizumab compared to fingolimod on the evolution of new on-treatment T1-gadolinium-enhancing (Gd+) lesions to persistent black holes (PBH) over 52 weeks. The secondary objectives of this study in this study population are to assess the effect of natalizumab compared to fingolimod on: magnetic resonance imaging (MRI) measures of central nervous system (CNS) tissue destruction as measured by the number of new T1-Gd+ lesions; various other MRI measures of disease activity; No Evidence of Disease Activity (NEDA); Relapse on treatment over 52 weeks; The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: natalizumab; Drug: fingolimod	Phase 4

Detailed Description

This study also includes a Diffusion Tensor Imaging (DTI) sub-study that includes healthy volunteers. Healthy volunteers will not receive any study medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-Label Study to Assess the Impact of Natalizumab Versus Fingolimod on Central Nervous System Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis Subjects
• Actual Study Start Date: Nov 30, 2014
• Actual Primary Completion Date: May 18, 2016
• Actual Study Completion Date: May 18, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: natalizumab Open-label natalizumab 300 mg IV every 4 weeks (Q4W)	Drug: natalizumab; Administered as specified in the treatment arm; Other Names: BG00002 Tysabri
Active Comparator: fingolimod Open-label fingolimod 0.5 mg once daily orally	Drug: fingolimod; Administered as specified in the treatment arm; Other Names: FTY720 Gilenya

Outcome Measures

Primary Outcome Measures

1. Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions [Up to Week 52]

Secondary Outcome Measures

1. Cumulative Number of New T1-Gd+ Lesions [Baseline, Week 4, Week 12, Week 24]

2. Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24 [Baseline, Week 24]

   As assessed by magnetic resonance imaging (MRI).

3. Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52 [Baseline, Week 52]

   As assessed by MRI.

4. Cumulative Number of New or Enlarging T2 Lesions [Baseline, Week 24]

5. Proportion of Participants With No Evidence of Disease Activity (NEDA) [Up to Week 52]

   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.

6. Time to First Relapse [Up to Week 52]

   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.

7. Cumulative Risk of Relapse [Up to Week 52]

   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.

8. Time to Complete Recovery From First Relapse [Up to Week 52]

   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.

9. Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24 [Baseline, Week 24]

   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.

10. Change From Baseline in SDMT at Week 52 [Baseline, Week 52]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria for MS Patients:

• Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria) at study screening with EDSS score from 0.0 to 5.5.

• If the subject is on Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and

Aubagio (BRACE-TA) at study screening:

• He/she must have been on therapy for at least 6 months (unless experiencing highly active disease), have at least 9 T2-hyperintense lesions on a brain MRI scan, and have experienced ≥1 relapse within the last 6 months prior to study screening with ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening

• If the subject has highly active disease, regardless of whether they are disease-modifying therapy (DMT)-naïve or had previous exposure to Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA), they must have had ≥2 disabling relapses in the 12 months prior to study screening and either ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening

Key Exclusion Criteria for MS Patients:

• Diagnosis of Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis.

• History or positive test result at study screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).

• Prior treatment with natalizumab or fingolimod.

• History of or known active malignant disease, including solid tumors and hematologic malignancies (subjects with cutaneous basal and squamous cell carcinoma that has been completely excised and considered cured prior to study screening remain eligible).

• History of opportunistic infections or any clinically significant major disease, as determined by the Investigator.

• A clinically significant infectious illness (e.g., pneumonia, septicemia) within the 1 month prior to study screening.

• History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.

• Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab), or exposure to intravenous immunoglobulin (IGIV), monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins in the last 12 months prior to study screening.

• History of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 months.

• Treatment with Class Ia (e.g., procainamide, quinidine, ajmaline, disopyramide) or Class III (amiodarone, bretylium, dofelitide, sotalol, ibulitide, azilimide) anti-arrhythmic drugs.

• Concurrent therapy with drugs that slow heart rate (e.g., beta-blockers, heart-rate lowering calcium channel blockers such as diltiazem or verapamil, or digoxin).

• Hypertension not controlled with prescribed medications.

• History of severe respiratory disease, pulmonary fibrosis or class III or IV chronic obstructive pulmonary disease.

• The use of live or live attenuated vaccination within 8 weeks of study screening.

Key Inclusion Criteria for Healthy Volunteers:

• Subjects who are generally healthy as demonstrated by physical examination and by medical history, with no history or evidence of major illnesses, diseases, or disorders.

• Subjects of childbearing potential must practice effective contraception and be willing and able to continue contraception for duration of the study.

• No history of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.

Key Exclusion Criteria for Healthy Volunteers:

• Claustrophobia sufficient to interfere with generating reliable MRI scans.

• History of other major illness including neurological disorders as determined by the Investigator.

• Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects), which would be a contraindication for MRI.

• Women who are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Aurora	Colorado	United States	80045
2	Research Site	Colorado Springs	Colorado	United States	80907
3	Research Site	Port Charlotte	Florida	United States	33952
4	Research Site	Atlanta	Georgia	United States	30327
5	Research Site	Des Moines	Iowa	United States	50314
6	Research Site	Philadelphia	Pennsylvania	United States	19104
7	Research Site	Knoxville	Tennessee	United States	37922
8	Research Site	Round Rock	Texas	United States	78681
9	Research Site	San Antonio	Texas	United States	78229
10	Research Site	Seattle	Washington	United States	98122
11	Research Site	Tacoma	Washington	United States	98405
12	Research Site	Milwaukee	Wisconsin	United States	53215
13	Research Site	Camperdown	New South Wales	Australia	2050
14	Research Site	New Lambton Heights	New South Wales	Australia	2305
15	Research Site	Heidelberg	Victoria	Australia	3084
16	Research Site	Brno		Czechia	625 00
17	Research Site	Brno		Czechia	656 91
18	Research Site	Hradec Kralove		Czechia	500 05
19	Research Site	Jihlava		Czechia	58633
20	Research Site	Ostrava - Poruba		Czechia	708 52
21	Research Site	Pardubice		Czechia	532 03
22	Research Site	Praha 5		Czechia	150 06
23	Research Site	Teplice		Czechia	415 01
24	Research Site	Nimes	Gard	France	30029
25	Research Site	Libourne Cedex	Gironde	France	33505
26	Research Site	Toulouse cedex 9	Haute Garonne	France	31059
27	Research Site	Freiburg	Baden Wuerttemberg	Germany	79106
28	Research Site	Erbach	Hessen	Germany	64711
29	Research Site	Gianicolense	Roma	Italy	87-00151
30	Research Site	Roma		Italy	00189
31	Research Site	El Palmar	Murcia	Spain	30120
32	Research Site	Malaga	Málaga	Spain	29010
33	Research Site	Vigo	Pontevedra	Spain	36204
34	Research Site	Santa Cruz de Tenerife	Tenerife	Spain	38010
35	Research Site	Barcelona		Spain	08035
36	Research Site	Girona		Spain	17007
37	Research Site	Madrid		Spain	28006
38	Research Site	Sevilla		Spain	E 41009
39	Research Site	Göteborg		Sweden	41345
40	Research Site	Stockholm		Sweden	17176
41	Research Site	London	Greater London	United Kingdom	SE5 9NU
42	Research Site	Glasgow	Strathclyde	United Kingdom	G51 4TF

Sponsors and Collaborators

• Biogen

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT02342704
• Other Study ID Numbers: 101MS408; 2013-004622-29
• First Posted: Jan 21, 2015
• Last Update Posted: Jun 9, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fingolimod Hydrochloride; Natalizumab

Study Results

Participant Flow

Pre-assignment Detail	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
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	54
COMPLETED	1	3
NOT COMPLETED	53	51

Baseline Characteristics

Arm/Group Title	Natalizumab	Fingolimod	Total
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 Participants	54	54	108
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.19 (8.811)	34.87 (8.731)	36.53 (8.887)
Sex: Female, Male (Count of Participants)
Female	37 68.5%	38 70.4%	75 69.4%
Male	17 31.5%	16 29.6%	33 30.6%

Outcome Measures

1. Primary Outcome

Title	Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions
Time Frame	Up to Week 52

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	0

2. Secondary Outcome

Title	Cumulative Number of New T1-Gd+ Lesions
Time Frame	Baseline, Week 4, Week 12, Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	Natalizumab	Fingolimod
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	47	45
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1260
	Comments
	Method	Wilcoxon rank-sum test
	Comments	p-value is based on Wilcoxon rank-sum test between the 2 treatment groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3525
	Comments
	Method	negative binomial regression
	Comments	p-value is based on negative binomial regression model, adjusted for baseline GD lesion count

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0127
	Comments
	Method	Wilcoxon rank-sum test
	Comments	p-value is based on Wilcoxon rank-sum test between the 2 treatment groups

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0299
	Comments
	Method	negative binomial regression
	Comments	p-value is based on negative binomial regression model, adjusted for baseline GD lesion count

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0123
	Comments
	Method	Wilcoxon rank-sum test
	Comments	p-value is based on Wilcoxon rank-sum test between the 2 treatment groups

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	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
Description	As assessed by magnetic resonance imaging (MRI).
Time Frame	Baseline, Week 24

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	15	16
T1 Lesion Volume Change	0.5 (31.235)	1.81 (19.703)
T2 Lesion Volume Change	0.08 (4.399)	3.32 (5.036)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	T1 Lesion Volume Change
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5318
	Comments
	Method	Wilcoxon rank-sum test
	Comments	p-value is based on Wilcoxon rank-sum test between the 2 treatment groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments	T2 Lesion Volume Change
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0528
	Comments
	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
Description	As assessed by MRI.
Time Frame	Baseline, Week 52

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	1
T1 Lesion Volume Change	-15.31 (NA)
T2 Lesion Volume Change	5.6 (NA)

5. Secondary Outcome

Title	Cumulative Number of New or Enlarging T2 Lesions
Time Frame	Baseline, Week 24

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	15	16
Mean (Standard Deviation) [lesions]	1.33 (2.469)	1.94 (2.205)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Natalizumab, Fingolimod
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2632
	Comments
	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)
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	0

7. Secondary Outcome

Title	Time to First Relapse
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	0

8. Secondary Outcome

Title	Cumulative Risk of Relapse
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	0

9. Secondary Outcome

Title	Time to Complete Recovery From First Relapse
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	14	17
Mean (Standard Deviation) [units on a scale]	3.79 (8.684)	3.24 (4.63)

11. Secondary Outcome

Title	Change From Baseline in SDMT at Week 52
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

Outcome Measure Data

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
Arm/Group Description	Open-label natalizumab 300 mg IV every 4 weeks	Open-label fingolimod 0.5 mg once daily orally
Measure Participants	0	9
Mean (Standard Deviation) [units on a scale]	2.11 (8.492)

Adverse Events

Time Frame	Up to 64 weeks.
Adverse Event Reporting Description	Treatment-emergent adverse events are presented.
Arm/Group Title	Natalizumab		Fingolimod
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Natalizumab		Fingolimod
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		2/54 (3.7%)
Cardiac disorders
Atrioventricular block second degree	0/54 (0%)		1/54 (1.9%)
Nervous system disorders
Migraine with aura	0/54 (0%)		1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	Natalizumab		Fingolimod
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/54 (25.9%)		23/54 (42.6%)
General disorders
Fatigue	3/54 (5.6%)		0/54 (0%)
Infections and infestations
Upper respiratory tract infection	1/54 (1.9%)		5/54 (9.3%)
Urinary tract infection	2/54 (3.7%)		3/54 (5.6%)
Investigations
Lymphocyte count decreased	0/54 (0%)		5/54 (9.3%)
Alanine aminotransferase increased	0/54 (0%)		3/54 (5.6%)
Nervous system disorders
Headache	6/54 (11.1%)		4/54 (7.4%)
Multiple sclerosis relapse	1/54 (1.9%)		8/54 (14.8%)
Hypoaesthesia	0/54 (0%)		3/54 (5.6%)
Migraine	0/54 (0%)		3/54 (5.6%)
Psychiatric disorders
Anxiety	1/54 (1.9%)		3/54 (5.6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/54 (5.6%)		1/54 (1.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.