Long-term Follow-up of Fingolimod Phase II Study Patients

Study Overview
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Brief Summary
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This study collected follow-up data on approximately 90% of participants who were randomized and received one dose of study drug in FTY720D2201 (D2201). No study drug was given or required. Participants were required to be assessed at one or two visits, preferably at the original study site, but the option to be interviewed via phone or seen at home was provided. Information was gathered also on deceased participants. Assessments were performed only once within an 8 week period and included medical history, Multiple Sclerosis (MS) and Multiple Sclerosis Disease Modifying Therapy (MS DMT) history, Expanded Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), and Multiple Sclerosis Functional Composite (MSFC).

Detailed Description
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This was a multicenter follow-up study of patients originally enrolled in the Phase 2 D2201 study. Patients did not receive any protocol specified treatment. The original D2201 study sites who agreed to participate in this study were required to locate their patients who were randomized in Study D2201 and asked them to return for a 10-year assessment, regardless of their current treatment status. Locating the patient may have required the use of search and advertising strategies to find those patients currently lost to follow-up, in accordance with local privacy legislation. Patients currently being followed within Study FTY720D2399 (NCT01201356) were asked to participate in Study FTY720D2201E2 and if patients gave consent, were enrolled concurrently in both studies.

Official Title
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Long-term Follow-up at 10 Years of Patients Enrolled in the Fingolimod Phase II Program in Relapsing Multiple Sclerosis (MS)

Conditions
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Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis

Intervention / Treatment
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* Other: Assessments arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Randomized in study FTY720D2201 and received at least one dose of study drug. Exclusion Criteria: None
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Phase 2 CFTY720D2201 (NCT02307838) participants<br>CFTY720D2201E2 participants did not receive any protocol specified treatment. The original D2201 study sites, who agreed to participate in this study, were required to locate their participants who were randomized in D2201 and asked them to return for a 10 year assessment, regardless of current treatment status. | Other: Assessments arm<br>* Protocol required assessments not provided in standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (BL) in Expanded Disability Status Scale (EDSS) | EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A negative change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disability Progression | Disability progression is defined as: 1.5-point increase from baseline in participants with baseline EDSS score = 0.0; OR 1-point increase in EDSS from baseline in participants with baseline EDSS score of 1.0 to 5.0 inclusive; OR 0.5-point increase in EDSS from baseline in participants with baseline EDSS score >5.0. | 10 Years | 
| Number of Participants With EDSS <4 or <6 | EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A positive change from baseline indicates improvement. | 10 years | 
| Number of Participants Not Using a Wheelchair or Being Bedridden | The number of participants not using a wheelchair or being bedridden was assessed. | 10 years | 
| Number of Participants Classified as Secondary Progressive MS (SPMS) | SPMS follows an initial relapsing-remitting course. Most people who are diagnosed with relapsing-remitting multiple sclerosis (RRMS) will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. Participants who were classified as SPMS were assessed. | 10 years | 
| Percentage of Participants With First Use of an Ambulatory Device | First use of an ambulatory device was considered from EDSS 6.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 6.0. | 10 years | 
| Percentage of Participants With First Use of a Wheelchair | First use of a wheelchair was considered from EDSS 7.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 7.0. | 10 years | 
| Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT) | The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and non-dominant hands are tested twice (two consecutive trials of the dominant hand, followed immediately by two consecutive trials of the non-dominant hand). The time limit per trial is 300 seconds. The right and left hand scores were the time in seconds it took to insert and remove 9 pegs ((the average scores from the four trials on the 9-HPT (the two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged)). A negative change from baseline indicates improvement. | baseline from core study, CFTY720D2201 (NCT00333138), 10 years | 
| Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score | The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The PASAT is the last measure administered at each visit. It is presented on audio compact disc (CD) to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test result is the number of correct sums given (out of 60 possible). A positive change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score | The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The patient is directed to one end of a clearly marked 25-foot (7.62 m) course and is instructed to walk 25 feet (7.62 meter) as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. The test scores were the time in seconds it took to walk the 25 feet. A negative change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score | MSFC is a composite measure encompassing information from the nine-hole peg test (arm dimension), timed 25 foot walk (leg dimension) and PASAT. The MSFC composite Z score was calculated as follows: (1) the average scores from the four trials on the 9-HPT (the two trials for each hand were averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals were averaged); (2) the average scores of two 25-Foot Timed Walk trials; (3) the number correct from the PASAT-3. The MSFC is based on the concept that scores for these three dimensions-arm, leg, and cognitive function are combined to create a single score (the MSFC) that can be used to detect change over time in a group of multiple sclerosis patients. This was done by creating Z-scores for each component of the MSFC, and averaging them to create an overall composite Z score. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Total Volume in T2 Lesion | Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). | 10 years | 
| Change From Baseline in Total Volume of T2 Lesion | Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Third Ventricle Diameter | Third ventricle diameter was assessed by MRI. | 10 years | 
| Change From Baseline in Third Ventricle Diameter | Third ventricle diameter was assessed by MRI. A negative change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Percentage Brain Volume Change (PBVC) | PVBC was assessed by MRI. A negative change from baseline indicates improvement. | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 
| Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | The correlation between FTY treatment duration and disability progression outcomes was assessed. The number presented in the table is the Pearson correlation coefficient, r. | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MS, RRMS, relapsing forms of multiple sclerosis, fingolimod, FTY720, Gilenya