Long-term Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Registration Number
- NCT00662649
- Lead Sponsor
- Novartis
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 920
- Patients should complete the 24 month core study
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo-fingolimod Fingolimod 0.5 mg 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. Placebo-fingolimod 0.5 mg Fingolimod 0.5 mg Patients randomized to placebo in the Core study were re randomized to fingolimod 0.5 mg/day in this Extension study. Placebo-fingolimod Fingolimod 1.25 mg 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. Placebo-fingolimod 1.25 mg Fingolimod 1.25 mg Patients randomized to placebo in the Core study were re randomized to fingolimod 1.25 mg/day in this Extension study. Fingolimod 1.25 mg Fingolimod 1.25 mg 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. Fingolimod 0.5 mg Fingolimod 0.5 mg Patients continued the same dose to which they had been randomized in the Core study, fingolimod 0.5 mg/day, in this Extension study.
- Primary Outcome Measures
Name Time Method Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) Months 0 to end of study (maximum up to 60 months) 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.
Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free Core baseline to end of study (maximum up to 60 months) 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.
Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) 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.
Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) 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.
- Secondary Outcome Measures
Name Time Method 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) 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.
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) 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.
Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) Months 0-24 (core study) and Months 24-48 (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.
Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) Months 0 to end of study (maximum up to 60 months) 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.
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 Core baseline to end of study (maximum up to 60 months) 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.
Trial Locations
- Locations (4)
Novartis Investigational Site
🇹🇷Yenisehir/Izmir, Turkey
Novaratis Investigative Site
🇮🇱Ashkelon, Israel
Novartis Investigative Site
🇬🇧Sheffield, United Kingdom
Austin Health, Department of Neurology
🇦🇺Heidelberg, Australia