Long-term Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis

Study Overview
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Brief Summary
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This extension study of was designed to evaluate the long-term safety, tolerability, and efficacy of fingolimod (FTY720) in patients with multiple sclerosis. The Extension study was an extension to the 24-month Core study (CFTY720D2301/NCT00289978).

Official Title
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An Extension of the 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing Efficacy and Safety of Fingolimod (FTY720) 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod 0.5 mg
* Drug: Fingolimod 1.25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should complete the 24 month core study Exclusion Criteria: Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc. Pregnant or nursing women Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 58 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod 1.25 mg<br>Patients continued the same dose to which they had been randomized in the Core study (CFTY720D2301/NCT00289978), fingolimod 1.25 mg/day, in this Extension study. | Drug: Fingolimod 1.25 mg<br>* Patients self-administered fingolimod 1.25 mg capsules orally once daily.<br>* Other names: FTY720;|
| Experimental: Fingolimod 0.5 mg<br>Patients continued the same dose to which they had been randomized in the Core study, fingolimod 0.5 mg/day, in this Extension study. | Drug: Fingolimod 0.5 mg<br>* Patients self-administered fingolimod 0.5 mg capsules orally once daily.<br>* Other names: FTY720;|
| Experimental: Placebo-fingolimod<br>Patients randomized to placebo in the Core study were re randomized to fingolimod (either 0.5 or 1.25 mg/day) in this Extension study. | Drug: Fingolimod 0.5 mg<br>* Patients self-administered fingolimod 0.5 mg capsules orally once daily.<br>* Other names: FTY720;Drug: Fingolimod 1.25 mg<br>* Patients self-administered fingolimod 1.25 mg capsules orally once daily.<br>* Other names: FTY720;|
| Experimental: Placebo-fingolimod 1.25 mg<br>Patients randomized to placebo in the Core study were re randomized to fingolimod 1.25 mg/day in this Extension study. | Drug: Fingolimod 1.25 mg<br>* Patients self-administered fingolimod 1.25 mg capsules orally once daily.<br>* Other names: FTY720;|
| Experimental: Placebo-fingolimod 0.5 mg<br>Patients randomized to placebo in the Core study were re randomized to fingolimod 0.5 mg/day in this Extension study. | Drug: Fingolimod 0.5 mg<br>* Patients self-administered fingolimod 0.5 mg capsules orally once daily.<br>* Other names: FTY720;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) | ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. | Months 0 to end of study (maximum up to 60 months) | 
| Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free | A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Kaplan-Meier estimates of the percentage of relapse-free patients at end of study and and 95% confidence intervals (CIs) were presented for the treatment groups. | Core baseline to end of study (maximum up to 60 months) | 
| Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. | Months 0-24 (core study) and Months 24-48 (extension study) | 
| Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) | ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. | Months 0-24 (core study) and Months 24-48 (extension study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Number of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | The number of new or newly enlarged T2 lesions was assessed with T2-weighted MRI scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2 weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis. | Months 0-24 (core study) and Months 24-48 (extension study) | 
| Percentage of Patients Free of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | The number of new or newly enlarged T2 lesions was assessed with T2-weighted MRI scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2 weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis. | Months 0-24 (core study) and Months 24-48 (extension study) | 
| Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | 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. | Months 0-24 (core study) and Months 24-48 (extension study) | 
| Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) | 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. | Months 0 to end of study (maximum up to 60 months) | 
| Time to First 3-month Confirmed Disability Progression up to End of Study Based on Expanded Disability Status Scale (EDSS): Kaplan-Meier Estimate of Percentage of Patients Free of Disability Progression | Kurtzke's Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in multiple sclerosis (MS) includes a series of scores in each of eight functional systems such as Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, Cerebral, and Other. The EDSS steps range from 0 (normal) to 10 (death due to MS). The Kaplan-Meier estimates of the percentage of participants free of disability progression at end of study and their 95% CIs were provided for each treatment group. | Core baseline to end of study (maximum up to 60 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis., Relapse-remitting, Fingolimod