Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis., Relapse-remitting, Fingolimod
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).
Interventions
Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 58 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Australia, Belgium, Canada, Czechia, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
Of the 1272 patients randomly assigned to treatment in the Core study (ClinicalTrials.gov ID NCT00289978), 1033 completed the 24-month double-blind treatment phase and were eligible to enter the Extension study. A total of 920 of the 1033 patients entered the Extension study and received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Fingolimod 1.25 mg Patients continued the same dose to which they had been randomized in the core study, fingolimod 1.25 mg/day, in this extension study. | 289 |
| 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. | 331 |
| Placebo-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. | 145 |
| Placebo-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. | 155 |
| Total | 920 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Core Study (24 Months) | Abnormal laboratory value(s) | 20 | 9 | 1 | 0 | 0 |
| Core Study (24 Months) | Abnormal test procedure result(s) | 2 | 1 | 1 | 0 | 0 |
| Core Study (24 Months) | Adverse Event | 22 | 13 | 18 | 0 | 0 |
| Core Study (24 Months) | Death | 1 | 0 | 2 | 0 | 0 |
| Core Study (24 Months) | Lost to Follow-up | 3 | 5 | 7 | 0 | 0 |
| Core Study (24 Months) | Protocol Violation | 5 | 5 | 4 | 0 | 0 |
| Core Study (24 Months) | Unsatisfactory therapeutic effect | 13 | 6 | 25 | 0 | 0 |
| Core Study (24 Months) | Withdrawal by Subject | 31 | 17 | 28 | 0 | 0 |
| Extension Study (Month 24 to 60) | Abnormal laboratory value(s) | 10 | 5 | 0 | 8 | 3 |
| Extension Study (Month 24 to 60) | Abnormal test procedure result(s) | 3 | 1 | 0 | 1 | 3 |
| Extension Study (Month 24 to 60) | Administrative problems | 0 | 0 | 0 | 1 | 0 |
| Extension Study (Month 24 to 60) | Adverse Event | 6 | 9 | 0 | 6 | 10 |
| Extension Study (Month 24 to 60) | Lost to Follow-up | 2 | 0 | 0 | 1 | 1 |
| Extension Study (Month 24 to 60) | Protocol Violation | 1 | 1 | 0 | 0 | 0 |
| Extension Study (Month 24 to 60) | Subject no longer requires study drug | 0 | 1 | 0 | 0 | 0 |
| Extension Study (Month 24 to 60) | Subject withdrew consent | 19 | 23 | 0 | 15 | 9 |
| Extension Study (Month 24 to 60) | Unsatisfactory therapeutic effect | 3 | 1 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Fingolimod 1.25 mg | Fingolimod 0.5 mg | Placebo-fingolimod 1.25 mg | Placebo-fingolimod 0.5 mg | Total |
|---|---|---|---|---|---|
| Age Continuous | 37.2 years STANDARD_DEVIATION 8.87 | 36.5 years STANDARD_DEVIATION 8.6 | 36.6 years STANDARD_DEVIATION 9.21 | 38.1 years STANDARD_DEVIATION 8.26 | 37.0 years STANDARD_DEVIATION 8.73 |
| Sex: Female, Male Female | 204 Participants | 234 Participants | 107 Participants | 106 Participants | 651 Participants |
| Sex: Female, Male Male | 85 Participants | 97 Participants | 38 Participants | 49 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 236 / 289 | 273 / 331 | 107 / 145 | 130 / 155 |
| serious Total, serious adverse events | 31 / 289 | 31 / 331 | 17 / 145 | 11 / 155 |
Outcome results
Primary
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.
Time frame: Months 0-24 (core study) and Months 24-48 (extension study)
Population: Extension intent-to-treat (ITT) population: All extension randomized patients that received at least 1 dose of extension study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fingolimod 1.25 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 0-24 | 0.064 Relapses per year |
| Fingolimod 1.25 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 24-48 | 0.074 Relapses per year |
| Fingolimod 0.5 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 24-48 | 0.095 Relapses per year |
| Fingolimod 0.5 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 0-24 | 0.111 Relapses per year |
| Placebo-fingolimod | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 0-24 | 0.301 Relapses per year |
| Placebo-fingolimod | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 24-48 | 0.164 Relapses per year |
| Placebo-fingolimod 0.5 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 0-24 | 0.292 Relapses per year |
| Placebo-fingolimod 0.5 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) | Months 24-48 | 0.130 Relapses per year |
Primary
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.
Time frame: Months 0 to end of study (maximum up to 60 months)
Population: Core Intent to treat (ITT) population: All patients who were randomized in the Core study and received at least 1 dose of Core study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fingolimod 1.25 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) | 0.164 Relapses per year |
| Fingolimod 0.5 mg | Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) | 0.185 Relapses per year |
| Placebo-fingolimod | Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) | 0.357 Relapses per year |
Primary
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.
Time frame: Months 0-24 (core study) and Months 24-48 (extension study)
Population: Extension intent-to-treat (ITT) population: All extension randomized patients that received at least 1 dose of extension study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fingolimod 1.25 mg | Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) | 1.164 Ratio of relapses per year |
| Fingolimod 0.5 mg | Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) | 0.850 Ratio of relapses per year |
| Placebo-fingolimod | Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) | 0.547 Ratio of relapses per year |
| Placebo-fingolimod 0.5 mg | Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) | 0.446 Ratio of relapses per year |
Primary
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.
Time frame: Core baseline to end of study (maximum up to 60 months)
Population: Core Intent to treat (ITT) population: All patients who were randomized in the Core study and received at least 1 dose of Core study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fingolimod 1.25 mg | Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free | 59.85 Percentage of patients |
| Fingolimod 0.5 mg | Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free | 59.29 Percentage of patients |
| Placebo-fingolimod | Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free | 37.18 Percentage of patients |
Secondary
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.
Time frame: Months 0-24 (core study) and Months 24-48 (extension study)
Population: Extension intent-to-treat (ITT) population: All extension randomized patients that received at least 1 dose of extension study drug. The analysis included number of patients with evaluable T2 MRI scans.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod 1.25 mg | 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 | 2.14 Lesions | Standard Deviation 5.234 |
| Fingolimod 1.25 mg | 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) | Change from Months 0-24 to Months 24-48 | -0.43 Lesions | Standard Deviation 4.393 |
| Fingolimod 1.25 mg | 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 24-48 | 1.71 Lesions | Standard Deviation 4.902 |
| Fingolimod 0.5 mg | 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 | 2.66 Lesions | Standard Deviation 9.395 |
| Fingolimod 0.5 mg | 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) | Change from Months 0-24 to Months 24-48 | -0.09 Lesions | Standard Deviation 7.423 |
| Fingolimod 0.5 mg | 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 24-48 | 2.58 Lesions | Standard Deviation 9.256 |
| Placebo-fingolimod | 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 24-48 | 2.34 Lesions | Standard Deviation 4.745 |
| Placebo-fingolimod | 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 | 12.83 Lesions | Standard Deviation 17.573 |
| Placebo-fingolimod | 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) | Change from Months 0-24 to Months 24-48 | -10.48 Lesions | Standard Deviation 15.98 |
| Placebo-fingolimod 0.5 mg | 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 | 8.12 Lesions | Standard Deviation 11.083 |
| Placebo-fingolimod 0.5 mg | 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) | Change from Months 0-24 to Months 24-48 | -6.68 Lesions | Standard Deviation 9.876 |
| Placebo-fingolimod 0.5 mg | 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 24-48 | 1.43 Lesions | Standard Deviation 2.446 |
Secondary
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.
Time frame: Months 0-24 (core study) and Months 24-48 (extension study)
Population: Extension intent-to-treat (ITT) population: All extension randomized patients that received at least 1 dose of extension study drug. The analysis included number of patients with evaluable T2 MRI scans.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fingolimod 1.25 mg | 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 24-48 | 57.1 Percentage of patients |
| Fingolimod 1.25 mg | 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 | 53.2 Percentage of patients |
| Fingolimod 0.5 mg | 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 24-48 | 69.3 Percentage of patients |
| Fingolimod 0.5 mg | 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 | 50.3 Percentage of patients |
| Placebo-fingolimod | 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 | 18.5 Percentage of patients |
| Placebo-fingolimod | 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 24-48 | 52.3 Percentage of patients |
| Placebo-fingolimod 0.5 mg | 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 | 23.2 Percentage of patients |
| Placebo-fingolimod 0.5 mg | 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 24-48 | 55.1 Percentage of patients |
Secondary
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.
Time frame: Months 0 to end of study (maximum up to 60 months)
Population: Core intent-to-treat (ITT) population: All patients who were randomized in the Core study and received at least 1 dose of Core study drug. This analysis included only patients with value at both core baseline and end of study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod 1.25 mg | Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) | -1.639 Percent change | Standard Deviation 1.9265 |
| Fingolimod 0.5 mg | Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) | -1.674 Percent change | Standard Deviation 2.1182 |
| Placebo-fingolimod | Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) | -2.241 Percent change | Standard Deviation 2.1873 |
Secondary
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.
Time frame: Months 0-24 (core study) and Months 24-48 (extension study)
Population: Extension intent-to-treat (ITT) population: All extension randomized patients that received at least 1 dose of extension study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod 1.25 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 0 to Month 24, n=75, 109, 41, 49 | -1.011 Percent change | Standard Deviation 1.3477 |
| Fingolimod 1.25 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 24 to Month 48, n=75, 109, 41, 49 | -0.871 Percent change | Standard Deviation 1.4164 |
| Fingolimod 0.5 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 24 to Month 48, n=75, 109, 41, 49 | -0.780 Percent change | Standard Deviation 1.9266 |
| Fingolimod 0.5 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 0 to Month 24, n=75, 109, 41, 49 | -0.983 Percent change | Standard Deviation 1.6291 |
| Placebo-fingolimod | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 0 to Month 24, n=75, 109, 41, 49 | -1.511 Percent change | Standard Deviation 1.6401 |
| Placebo-fingolimod | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 24 to Month 48, n=75, 109, 41, 49 | -1.103 Percent change | Standard Deviation 1.4073 |
| Placebo-fingolimod 0.5 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 0 to Month 24, n=75, 109, 41, 49 | -1.419 Percent change | Standard Deviation 1.3923 |
| Placebo-fingolimod 0.5 mg | Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) | Month 24 to Month 48, n=75, 109, 41, 49 | -0.903 Percent change | Standard Deviation 1.1406 |
Secondary
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.
Time frame: Core baseline to end of study (maximum up to 60 months)
Population: Core intent-to-treat (ITT) population: All patients who were randomized in the Core study and received at least 1 dose of Core study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fingolimod 1.25 mg | 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 | 74.15 Percentage of patients |
| Fingolimod 0.5 mg | 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 | 73.90 Percentage of patients |
| Placebo-fingolimod | 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 | 66.28 Percentage of patients |