Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Study Overview
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Brief Summary
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This study assessed the safety, tolerability, and efficacy of 2 doses of oral fingolimod versus interferon β-1a to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis.

Official Title
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A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekly in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod 1.25 mg
* Drug: Fingolimod 0.5 mg
* Drug: Interferon β-1a 30 µg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis (MS) Patients with a relapsing-remitting disease course Patients with Expanded Disability Status Scale (EDSS) score of 0-5.5 Exclusion Criteria: Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc Pregnant or nursing women Patients who cannot tolerate treatment with an interferon Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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> | Drug: Fingolimod 1.25 mg<br>* Core: Patients self-administered fingolimod 1.25 mg capsules orally once daily. In addition, they self-administered an interferon β-1a placebo intramuscular (im) injection once weekly. Extension: Patients self-administered fingolimod 1.25 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.<br>* Other names: FTY720;|
| Experimental: Fingolimod 0.5 mg<br> | Drug: Fingolimod 0.5 mg<br>* Core: Patients self-administered fingolimod 0.5 mg capsules orally once daily. In addition, they self-administered an interferon β-1a placebo intramuscular (im) injection once weekly. Extension: Patients self-administered fingolimod 0.5 mg capsules orally once daily.<br>* Other names: FTY720;|
| Active Comparator: Interferon β-1a 30 µg<br> | Drug: Interferon β-1a 30 µg<br>* Core: Patients self-administered interferon β-1a 30 μg in an intramuscular (im) injection once weekly. In addition, they self-administered a fingolimod placebo capsule orally once daily. Extension: Patients self-administered either fingolimod 1.25 mg or 0.5 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study | The 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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score. | Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study | The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (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. | Baseline to Month 12 | 
| Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study | The 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. | Baseline to Month 12 | 
| Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study | The 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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score. | Month 0 to end of study (up to approximately 4.5 years) | 
| Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study | The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (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. | Month 12 to end of study (up to approximately 3.5 years) | 
| Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study | The 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. | Baseline to end of study (up to approximately 4.5 years) | 

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