Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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This study evaluated the safety, tolerability and effect on MRI lesion parameters of FTY720 in patients with relapsing multiple sclerosis.

Official Title
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Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Evaluating the Safety, Tolerability and Effect on MRI Lesion Parameters of FTY720 vs Placebo in Patients With Relapsing Multiple Sclerosis Including 18 Month Extension Phase

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: FTY720
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Core Study Inclusion Criteria: Diagnosis of relapsing multiple Sclerosis (MS) Patients with at least two documented relapses in the previous 2 years or one documented relapse in the last year Patients with an Expanded Disability Status Scale (EDSS) score of 0-6 Extension Study A positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening was negative, a second scan could have been obtained 1 month later) Neurologically stable with no evidence of relapse within 30 days prior to randomization,or during the Screening and Baseline periods. Female patients either post-menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control. Females of childbearing potential with a negative pregnancy test at baseline prior to entry into the treatment period. Exclusion Criteria: Core Study Patients with other chronic disease of the immune system, malignancies, pulmonary or heart disease, etc Pregnant or nursing women Extension Study Patients who had permanently discontinued study drug prior to the Month 6 visit of the core study Patients with diabetes mellitus (to reduce the risk of ME), and therefore ongoing patients with diabetes mellitus or who developed diabetes mellitus were discontinued from the study) Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod (FTY720) 1.25 mg/day<br>Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | Drug: FTY720<br>* FTY720 capsule was taken orally once a day<br>|
| Placebo Comparator: Placebo/Fingolimod (FTY720)<br>Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | Drug: Placebo<br>* Placebo 1.25 mg capsule was given once daily<br>|
| Experimental: Fingolimod (FTY720) 5.0 mg/day<br>Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 15 to 24 months 1.25mg once daily. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | Drug: FTY720<br>* FTY720 capsule was taken orally once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) | 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. | Month 6 (Core) | 
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 | 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. | Month 12 (extension) | 
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 | 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. | Month 60 (extension) | 
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study | 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. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | Last observation (Up to 80 months in average) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Free of T1-weighted Lesions | A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average) | 
| Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | Month 6 and 12, 60, last observation (up to 80 months in average) | 
| Mean Number of New T2-weighted Lesions | New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) | 
| Volume of T2-weighted Lesions | Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) | 
| Change From Baseline in Volume of Total T2-weighted 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). The last observation was the last observation available for each patient which ranged from 1 to 2801 days. | Baseline to month 6, 12, 60 and Last observation (up to 80 months in average) | 
| Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | The Expanded Disability Status Scale (EDSS) is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method. The last observation was the last observation available for each patient which ranged from 1 to 2801 days | Month 6,12,60 and Last observation (up to 80 months in average) | 
| Mean Trough Blood Concentrations of FTY720 | For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients. | Month 3 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, FTY720, Multiple Sclerosis, RRMS