An Extension Study of the Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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This study was an extension study of NCT00537082. This study was designed to evaluate the efficacy and safety of long-term administration of 0.5 mg or 1.25 mg of fingolimod (FTY720) to relapsing multiple sclerosis.

Detailed Description
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A decision was made to switch all patients on fingolimod 1.25 mg/day to fingolimod 0.5 mg/day in an amendment to the study protocol. The study became open-label with all patients receiving fingolimod 0.5 mg/day on 22 Feb 2010. The efficacy data for Months 0-6 in this study report is from the core study NCT00537082.

Official Title
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An Extension of the 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who completed 6 months of treatment with the study drug and the Month 6 visit in the core study NCT00537082. Females of childbearing potential who have a negative pregnancy test in the core study NCT00537082. Exclusion Criteria: Patients who permanently discontinued study drug treatment prior to the Month 6 visit in the core study NCT00537082. Other protocol-defined inclusion/exclusion criteria applied to the study.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod 0.5 mg<br>Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study. | Drug: Fingolimod<br>* Fingolimod was supplied in capsules.<br>* Other names: Imsera;|
| Experimental: Fingolimod 1.25 mg<br>Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study. | Drug: Fingolimod<br>* Fingolimod was supplied in capsules.<br>* Other names: Imsera;|
| Experimental: Placebo-fingolimod<br>Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study. | Drug: Fingolimod<br>* Fingolimod was supplied in capsules.<br>* Other names: Imsera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions | To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion. | Months 6, 9, 12, 18, 24, 36, and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions | To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion. | Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years) | 
| Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses | The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (< 37.5°C) or infection. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS). | Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years) | 
| Percentage of Patients Relapse-free at the End of the Study | Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients. | Baseline to the end of the study (up to 4 years) | 
| Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment | Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months. | Baseline to the end of the study (up to 4 years) | 
| Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score | Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months. | Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FTY720, multiple sclerosis, MS