Back to resultsFingolimod Versus Interferon Beta 1b in Cognitive Symptoms (Cognition)
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Fingolimod
Interferon beta 1b
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, cognitive symptoms, relapsing-remitting multiple sclerosis (RRMS), fingolimod, Magnetic resonance imaging (MRI)
Eligibility Criteria
Inclusion Criteria:
- Patients with relapsing-remitting forms of MS defined by 2005 revised McDonald criteria.
- Patients with active disease, defined as at least one clinical relapse in the last year, or two clinical relapses in the last two years if there are signs of disease activity at one brain MRI scan performed in the last six months.
- Patients with cognitive impairment at screening, defined as at least one test of the Rao's Brief Repeatable Battery with scores falling outside the 90th percentile of the normative data.
Exclusion Criteria:
- Patients who had already been treated with multiweekly interferon (interferon beta 1b, or beta 1a multiweekly) and had an unsatisfactory response according to the judgment of the investigator.
- Patients with hyperactive forms of the MS disease according to the judgment of the investigator.
- Patients with an EDSS score higher than 5.
- Patients with a prior or current diagnosis of Major Depression according to DSM-IV.
- Patients with a history of chronic disease of the immune system other than MS such as known immunodeficiency syndrome.
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fingolimod
Interferon beta 1b
Arm Description
0.5 mg in capsules for oral administration once daily
250 μg injected s.c. every other day
Outcomes
Primary Outcome Measures
Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change From Screening in Spatial Recall Test (SPART) Raw Score
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern is shown to the subject for ten seconds. The subject is then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score is the total number of correct responses for the tree trials. The total score ranged from 0 to 30. Higher values represent a better outcome.
Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score
Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. It presents a series of nine symbols, each of which is paired with a single digit labeled 1-9 in a key at the top of the sheet. The reminder of the page has a pseudo-randomized sequence of symbols, and the patient must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome.
Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 3 seconds in the first part of the test (PASAT-3). The patient is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.
Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 2 seconds in the second part of the test (PASAT-2). The patient was asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.
Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score
The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). The Delayed SRT test is the total number of words recalled after a delayed period. The total score ranged from 0 to 12. Higher values represent a better outcome.
Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern was shown to the subject for ten seconds. The subject was then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score was the total number of correct responses for the tree trials. The total score ranged from 0 to 10. Higher values represent a better outcome.
Change From Screening in Word List Generation (WLG)
Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. The test assessed the verbal fluency, recorded all the possible correct word that a patients should give in 90 sec. No maximum range is available. Higher values represent a better outcome. The score was the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, , but it is not a score scale.
Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 16. Higher values represent a better outcome
Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome
Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Secondary Outcome Measures
Change From Screening in the Volume of Total T2 Lesions
Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume
Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).
Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54)
A 54 question measure covers 12 domains; assesses mental and physical health. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. Each domain has a range from 0 to 100 where higher means better.
Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains).
Modified Fatigue Impact Scale (mFIS) questionnaire is described at each time point to evaluate fatigue by means of usual descriptive statistics. Three domains were also defined: Physical Subscale (sum of items 4, 6, 7, 10, 13, 14, 17, 20, 21 and therefore ranging from 0 to 36), Cognitive Subscale (sum of items 1, 2, 3, 5, 11, 12, 15, 16, 18, 19 and therefore ranging from 0 to 40) and Psychosocial Subscale (sum of items 8, 9 and therefore ranging from 0 to 8). Finally, mFIS - overall score ranged from 0 to 80. The mFIS total score was computed as the sum of scores for each item. Lower values represent a better outcome.
Change From Screening in the Number of New T2 Lesions
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (visit 8 to 18 month) is calculated as the sum of the number of lesions.
Change From Screening in the Volume of Total T1 Hypointense Lesions
Volume of hypointense post-gadolinium T1 lesion component was measured by MRI scan. Means were estimated using a Mixed-effect model with repeated measures (MMRM) by-visit interaction.
Change From Screening in the Number of T1 Gd+ Enhancing Lesions
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis
Change From Screening in the Percentage of Brain Volume Change
Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change.
Changes in the Environmental Status Scale Score (ESS)
The Environmental Status Scale (ESS) is used to quickly evaluate a patient for handicap. It was derived from a measure of socio-economic status. It consists of seven parameters: (1) actual work status, (2) financial and economic status, (3) personal residence or home, (4) personal assistance required, (5) transportation, (6) community services, (7) social activity. Each parameter has a single score from minimum 0 to maximum 5. ESS score is the sum of the points for all 7 parameters: minimum score: 0; maximum score: 35. The higher the score the greater the handicap
Full Information
NCT ID
NCT01333501
First Posted
April 8, 2011
Last Updated
January 30, 2017
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01333501
Brief Title
Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms
Acronym
Cognition
Official Title
A 18-month, Open-label, Rater-blinded, Randomized, Multi-center, Active-controlled, Parallel-group Pilot Study to Assess Efficacy and Safety of Fingolimod in Comparison to Interferon Beta 1b in Treating the Cognitive Symptoms Associated to Relapsing-remitting Multiple Sclerosis and to Assess Possible Relationship of These Effects to Regional Brain Atrophy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
The purpose of this pilot study is to evaluate, by means of a specific cognitive test battery (Brief Repeatable Battery and Delis-Kaplan Executive Function System scale), the slowing/reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment, and to evaluate which test of the battery is the most sensitive in detecting differences between treatment groups.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple sclerosis, cognitive symptoms, relapsing-remitting multiple sclerosis (RRMS), fingolimod, Magnetic resonance imaging (MRI)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
151 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fingolimod
Arm Type
Experimental
Arm Description
0.5 mg in capsules for oral administration once daily
Arm Title
Interferon beta 1b
Arm Type
Active Comparator
Arm Description
250 μg injected s.c. every other day
Intervention Type
Drug
Intervention Name(s)
Fingolimod
Intervention Description
0.5 mg in capsules for oral administration once daily
Intervention Type
Drug
Intervention Name(s)
Interferon beta 1b
Intervention Description
250 μg injected s.c. every other day
Primary Outcome Measure Information:
Title
Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score
Description
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score
Description
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Spatial Recall Test (SPART) Raw Score
Description
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern is shown to the subject for ten seconds. The subject is then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score is the total number of correct responses for the tree trials. The total score ranged from 0 to 30. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score
Description
Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. It presents a series of nine symbols, each of which is paired with a single digit labeled 1-9 in a key at the top of the sheet. The reminder of the page has a pseudo-randomized sequence of symbols, and the patient must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score
Description
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 3 seconds in the first part of the test (PASAT-3). The patient is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score
Description
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 2 seconds in the second part of the test (PASAT-2). The patient was asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score
Description
The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). The Delayed SRT test is the total number of words recalled after a delayed period. The total score ranged from 0 to 12. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)
Description
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern was shown to the subject for ten seconds. The subject was then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score was the total number of correct responses for the tree trials. The total score ranged from 0 to 10. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Word List Generation (WLG)
Description
Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. The test assessed the verbal fluency, recorded all the possible correct word that a patients should give in 90 sec. No maximum range is available. Higher values represent a better outcome. The score was the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, , but it is not a score scale.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2
Description
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 16. Higher values represent a better outcome
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2
Description
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2
Description
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Time Frame
Screening (-1month), 18 month
Secondary Outcome Measure Information:
Title
Change From Screening in the Volume of Total T2 Lesions
Description
Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume
Time Frame
Screening (-1 month), 18 months
Title
Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS)
Description
MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).
Time Frame
Screening (-1month), 18 month
Title
Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54)
Description
A 54 question measure covers 12 domains; assesses mental and physical health. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. Each domain has a range from 0 to 100 where higher means better.
Time Frame
Baseline, 18 months
Title
Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains).
Description
Modified Fatigue Impact Scale (mFIS) questionnaire is described at each time point to evaluate fatigue by means of usual descriptive statistics. Three domains were also defined: Physical Subscale (sum of items 4, 6, 7, 10, 13, 14, 17, 20, 21 and therefore ranging from 0 to 36), Cognitive Subscale (sum of items 1, 2, 3, 5, 11, 12, 15, 16, 18, 19 and therefore ranging from 0 to 40) and Psychosocial Subscale (sum of items 8, 9 and therefore ranging from 0 to 8). Finally, mFIS - overall score ranged from 0 to 80. The mFIS total score was computed as the sum of scores for each item. Lower values represent a better outcome.
Time Frame
Baseline, 18 months
Title
Change From Screening in the Number of New T2 Lesions
Description
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (visit 8 to 18 month) is calculated as the sum of the number of lesions.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in the Volume of Total T1 Hypointense Lesions
Description
Volume of hypointense post-gadolinium T1 lesion component was measured by MRI scan. Means were estimated using a Mixed-effect model with repeated measures (MMRM) by-visit interaction.
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in the Number of T1 Gd+ Enhancing Lesions
Description
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis
Time Frame
Screening (-1month), 18 month
Title
Change From Screening in the Percentage of Brain Volume Change
Description
Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change.
Time Frame
Screening (-1month), 18 month
Title
Changes in the Environmental Status Scale Score (ESS)
Description
The Environmental Status Scale (ESS) is used to quickly evaluate a patient for handicap. It was derived from a measure of socio-economic status. It consists of seven parameters: (1) actual work status, (2) financial and economic status, (3) personal residence or home, (4) personal assistance required, (5) transportation, (6) community services, (7) social activity. Each parameter has a single score from minimum 0 to maximum 5. ESS score is the sum of the points for all 7 parameters: minimum score: 0; maximum score: 35. The higher the score the greater the handicap
Time Frame
Baseline, 18 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with relapsing-remitting forms of MS defined by 2005 revised McDonald criteria.
Patients with active disease, defined as at least one clinical relapse in the last year, or two clinical relapses in the last two years if there are signs of disease activity at one brain MRI scan performed in the last six months.
Patients with cognitive impairment at screening, defined as at least one test of the Rao's Brief Repeatable Battery with scores falling outside the 90th percentile of the normative data.
Exclusion Criteria:
Patients who had already been treated with multiweekly interferon (interferon beta 1b, or beta 1a multiweekly) and had an unsatisfactory response according to the judgment of the investigator.
Patients with hyperactive forms of the MS disease according to the judgment of the investigator.
Patients with an EDSS score higher than 5.
Patients with a prior or current diagnosis of Major Depression according to DSM-IV.
Patients with a history of chronic disease of the immune system other than MS such as known immunodeficiency syndrome.
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Alzenau
ZIP/Postal Code
63755
Country
Germany
Facility Name
Novartis Investigative Site
City
Bamberg
ZIP/Postal Code
96049
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Bari
State/Province
BA
ZIP/Postal Code
70124
Country
Italy
Facility Name
Novartis Investigative Site
City
Bergamo
State/Province
BG
ZIP/Postal Code
24128
Country
Italy
Facility Name
Novartis Investigative Site
City
Montichiari
State/Province
BS
ZIP/Postal Code
25018
Country
Italy
Facility Name
Novartis Investigative Site
City
Chieti
State/Province
CH
ZIP/Postal Code
66100
Country
Italy
Facility Name
Novartis Investigative Site
City
Catania
State/Province
CT
ZIP/Postal Code
95122
Country
Italy
Facility Name
Novartis Investigative Site
City
Catania
State/Province
CT
ZIP/Postal Code
95123
Country
Italy
Facility Name
Novartis Investigative Site
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Novartis Investigative Site
City
Pozzilli
State/Province
IS
ZIP/Postal Code
86077
Country
Italy
Facility Name
Novartis Investigative Site
City
Messina
State/Province
ME
ZIP/Postal Code
98121
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Cefalù
State/Province
PA
ZIP/Postal Code
90015
Country
Italy
Facility Name
Novartis Investigative Site
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00133
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00179
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00189
Country
Italy
Facility Name
Novartis Investigative Site
City
Gallarate
State/Province
VA
ZIP/Postal Code
21013
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80138
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms
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