Multiple Sclerosis
Conditions
Keywords
FTY720, MS, Multiple Sclerosis, RRMS
Brief summary
This study evaluated the safety, tolerability and effect on MRI lesion parameters of FTY720 in patients with relapsing multiple sclerosis.
Interventions
DRUGFTY720
FTY720 capsule was taken orally once a day
DRUGPlacebo
Placebo 1.25 mg capsule was given once daily
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Core Study Inclusion Criteria: * Diagnosis of relapsing multiple Sclerosis (MS) * Patients with at least two documented relapses in the previous 2 years or one documented relapse in the last year * Patients with an Expanded Disability Status Scale (EDSS) score of 0-6 Extension Study * A positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening was negative, a second scan could have been obtained 1 month later) * Neurologically stable with no evidence of relapse within 30 days prior to randomization,or during the Screening and Baseline periods. * Female patients either post-menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control. Females of childbearing potential with a negative pregnancy test at baseline prior to entry into the treatment period.
Exclusion criteria
Core Study * Patients with other chronic disease of the immune system, malignancies, pulmonary or heart disease, etc * Pregnant or nursing women Extension Study * Patients who had permanently discontinued study drug prior to the Month 6 visit of the core study * Patients with diabetes mellitus (to reduce the risk of ME), and therefore ongoing patients with diabetes mellitus or who developed diabetes mellitus were discontinued from the study) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) | Month 6 (Core) | Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. |
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 | Month 12 (extension) | Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. |
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 | Month 60 (extension) | Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. |
| Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study | Last observation (Up to 80 months in average) | Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Volume of Total T2-weighted Lesions | Baseline to month 6, 12, 60 and Last observation (up to 80 months in average) | Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume). The last observation was the last observation available for each patient which ranged from 1 to 2801 days. |
| Percentage of Participants Free of T1-weighted Lesions | Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average) | A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
| Mean Trough Blood Concentrations of FTY720 | Month 3 and 6 | For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients. |
| Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | Month 6,12,60 and Last observation (up to 80 months in average) | The Expanded Disability Status Scale (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. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
| Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 6 and 12, 60, last observation (up to 80 months in average) | A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
| Mean Number of New T2-weighted Lesions | (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) | New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
| Volume of T2-weighted Lesions | (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) | Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days |
Countries
Canada, Denmark, Finland, France, Germany, Italy, Poland, Portugal, Spain, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | 93 |
| Fingolimod (FTY720) 1.25 mg/Day Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | 94 |
| Fingolimod (FTY720) 5.0 mg/Day Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation. | 94 |
| Total | 281 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Study (6 Months) | Adverse Event | 4 | 5 | 8 |
| Core Study (6 Months) | Laboratory abnormality | 0 | 0 | 1 |
| Core Study (6 Months) | Lack of Efficacy | 1 | 0 | 0 |
| Core Study (6 Months) | Protocol Violation | 1 | 0 | 1 |
| Core Study (6 Months) | Withdrawal by Subject | 1 | 1 | 2 |
| Extension Study (Month6 to End of Study) | Abnormal laboratory value | 3 | 2 | 2 |
| Extension Study (Month6 to End of Study) | Administrative problems | 1 | 1 | 2 |
| Extension Study (Month6 to End of Study) | Adverse Event | 15 | 19 | 15 |
| Extension Study (Month6 to End of Study) | Death | 0 | 1 | 0 |
| Extension Study (Month6 to End of Study) | Lack of Efficacy | 7 | 4 | 7 |
| Extension Study (Month6 to End of Study) | Lost to Follow-up | 1 | 1 | 0 |
| Extension Study (Month6 to End of Study) | Patient no longer required study drug | 2 | 1 | 0 |
| Extension Study (Month6 to End of Study) | Protocol Violation | 0 | 0 | 3 |
| Extension Study (Month6 to End of Study) | Withdrawal by Subject | 14 | 13 | 14 |
Baseline characteristics
| Characteristic | Placebo | Fingolimod (FTY720) 1.25 mg/Day | Fingolimod (FTY720) 5.0 mg/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 37.0 Years STANDARD_DEVIATION 8.8 | 38.1 Years STANDARD_DEVIATION 9.54 | 38.3 Years STANDARD_DEVIATION 10.51 | 37.8 Years STANDARD_DEVIATION 9.63 |
| Sex: Female, Male Female | 62 Participants | 71 Participants | 66 Participants | 199 Participants |
| Sex: Female, Male Male | 31 Participants | 23 Participants | 28 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 86 / 93 | 88 / 94 | 92 / 94 |
| serious Total, serious adverse events | 25 / 93 | 19 / 94 | 32 / 94 |
Outcome results
Primary
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: Last observation (Up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study | 0.8 GD- enhanced T1 lesions | Standard Deviation 2.87 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study | 0.4 GD- enhanced T1 lesions | Standard Deviation 1.39 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study | 0.5 GD- enhanced T1 lesions | Standard Deviation 1.65 |
Primary
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Time frame: Month 12 (extension)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 | 0.4 GD- enhanced T1 lesions | Standard Deviation 0.95 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 | 1.0 GD- enhanced T1 lesions | Standard Deviation 5.81 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 | 0.2 GD- enhanced T1 lesions | Standard Deviation 0.47 |
Primary
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Time frame: Month 60 (extension)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 | 0.2 GD- enhanced T1 lesions | Standard Deviation 0.7 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 | 0.2 GD- enhanced T1 lesions | Standard Deviation 0.92 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 | 0.1 GD- enhanced T1 lesions | Standard Deviation 0.55 |
Primary
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core)
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Time frame: Month 6 (Core)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) | 2.3 GD- enhanced T1 lesions | Standard Deviation 4.23 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) | 1.4 GD- enhanced T1 lesions | Standard Deviation 5.69 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) | 0.4 GD- enhanced T1 lesions | Standard Deviation 0.82 |
Secondary
Change From Baseline in Volume of Total T2-weighted Lesions
Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume). The last observation was the last observation available for each patient which ranged from 1 to 2801 days.
Time frame: Baseline to month 6, 12, 60 and Last observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The n in each category indicates participants with T2 information recorded at specific timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Volume of Total T2-weighted Lesions | Month 60 (extension) n=45, 49, 43 | -621.82 mm^3 | Standard Deviation 1338.966 |
| Placebo | Change From Baseline in Volume of Total T2-weighted Lesions | Month 6 (core) n=85, 89, 86 | 146.15 mm^3 | Standard Deviation 1683.602 |
| Placebo | Change From Baseline in Volume of Total T2-weighted Lesions | Last observation (extension) n= 87, 89, 87 | -178.86 mm^3 | Standard Deviation 1884.904 |
| Placebo | Change From Baseline in Volume of Total T2-weighted Lesions | Month 12 (extension) n=73, 77, 71 | 144.96 mm^3 | Standard Deviation 1513.577 |
| Fingolimod (FTY720) 1.25 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 60 (extension) n=45, 49, 43 | -204.09 mm^3 | Standard Deviation 2238.182 |
| Fingolimod (FTY720) 1.25 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 12 (extension) n=73, 77, 71 | 1.66 mm^3 | Standard Deviation 1714.731 |
| Fingolimod (FTY720) 1.25 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 6 (core) n=85, 89, 86 | -115.81 mm^3 | Standard Deviation 1031.799 |
| Fingolimod (FTY720) 1.25 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Last observation (extension) n= 87, 89, 87 | -92.24 mm^3 | Standard Deviation 3033.041 |
| Fingolimod (FTY720) 5.0 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 12 (extension) n=73, 77, 71 | -513.35 mm^3 | Standard Deviation 1943.338 |
| Fingolimod (FTY720) 5.0 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 6 (core) n=85, 89, 86 | -607.97 mm^3 | Standard Deviation 1705.486 |
| Fingolimod (FTY720) 5.0 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Last observation (extension) n= 87, 89, 87 | -907.48 mm^3 | Standard Deviation 2997.668 |
| Fingolimod (FTY720) 5.0 mg/Day | Change From Baseline in Volume of Total T2-weighted Lesions | Month 60 (extension) n=45, 49, 43 | -1429.98 mm^3 | Standard Deviation 3928.944 |
Secondary
Mean Number of New T2-weighted Lesions
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The n in each category indicates participants with T2 information recorded at specific timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of New T2-weighted Lesions | Month 6 (Core), n= 82,88, 84 | 1.0 GD enhanced T2 lesions | Standard Deviation 2.37 |
| Placebo | Mean Number of New T2-weighted Lesions | Month 12 (Extension) n=71, 79, 71 | 0.8 GD enhanced T2 lesions | Standard Deviation 1.41 |
| Placebo | Mean Number of New T2-weighted Lesions | Month 60 (Extension) n=45, 50, 43 | 0.4 GD enhanced T2 lesions | Standard Deviation 1.25 |
| Placebo | Mean Number of New T2-weighted Lesions | Last observation (Extension) n=92, 93, 91 | 0.7 GD enhanced T2 lesions | Standard Deviation 1.99 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of New T2-weighted Lesions | Last observation (Extension) n=92, 93, 91 | 0.6 GD enhanced T2 lesions | Standard Deviation 1.51 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of New T2-weighted Lesions | Month 6 (Core), n= 82,88, 84 | 0.5 GD enhanced T2 lesions | Standard Deviation 2.07 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of New T2-weighted Lesions | Month 60 (Extension) n=45, 50, 43 | 0.5 GD enhanced T2 lesions | Standard Deviation 1.36 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Number of New T2-weighted Lesions | Month 12 (Extension) n=71, 79, 71 | 1.4 GD enhanced T2 lesions | Standard Deviation 5.56 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of New T2-weighted Lesions | Last observation (Extension) n=92, 93, 91 | 0.5 GD enhanced T2 lesions | Standard Deviation 1.64 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of New T2-weighted Lesions | Month 12 (Extension) n=71, 79, 71 | 0.6 GD enhanced T2 lesions | Standard Deviation 1.1 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of New T2-weighted Lesions | Month 60 (Extension) n=45, 50, 43 | 0.3 GD enhanced T2 lesions | Standard Deviation 0.97 |
| Fingolimod (FTY720) 5.0 mg/Day | Mean Number of New T2-weighted Lesions | Month 6 (Core), n= 82,88, 84 | 0.1 GD enhanced T2 lesions | Standard Deviation 0.34 |
Secondary
Mean Trough Blood Concentrations of FTY720
For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients.
Time frame: Month 3 and 6
Population: Pharmacokinetics population included all the patients who had sample collected and analysis was performed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Trough Blood Concentrations of FTY720 | Month 3 (core) | 7.64 ng/mL | Standard Deviation 5.44 |
| Placebo | Mean Trough Blood Concentrations of FTY720 | Month 6 (core) | 7.38 ng/mL | Standard Deviation 4.57 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Trough Blood Concentrations of FTY720 | Month 3 (core) | 30.5 ng/mL | Standard Deviation 18.8 |
| Fingolimod (FTY720) 1.25 mg/Day | Mean Trough Blood Concentrations of FTY720 | Month 6 (core) | 28.9 ng/mL | Standard Deviation 22.1 |
Secondary
Percentage of Participants Free of T1-weighted Lesions
A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis. The n in each category indicates number of patients wih information recorded at scan
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Free of T1-weighted Lesions | Month 60 (Extension) n= 45, 49, 44 | 91.1 percentage of participants |
| Placebo | Percentage of Participants Free of T1-weighted Lesions | Month 12 (Extension) n= 72, 77, 71 | 79.2 percentage of participants |
| Placebo | Percentage of Participants Free of T1-weighted Lesions | Baseline (Core) n=93, 92, 93 | 49.5 percentage of participants |
| Placebo | Percentage of Participants Free of T1-weighted Lesions | Month 6 (Core) n= 83, 90, 87 | 47.0 percentage of participants |
| Placebo | Percentage of Participants Free of T1-weighted Lesions | Last observation (Extension) n= 92, 93, 92 | 81.5 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 12 (Extension) n= 72, 77, 71 | 83.1 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Baseline (Core) n=93, 92, 93 | 52.2 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 6 (Core) n= 83, 90, 87 | 76.7 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 60 (Extension) n= 45, 49, 44 | 91.8 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Last observation (Extension) n= 92, 93, 92 | 83.9 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Last observation (Extension) n= 92, 93, 92 | 83.7 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 60 (Extension) n= 45, 49, 44 | 93.2 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Baseline (Core) n=93, 92, 93 | 48.4 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 12 (Extension) n= 72, 77, 71 | 88.7 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Participants Free of T1-weighted Lesions | Month 6 (Core) n= 83, 90, 87 | 78.2 percentage of participants |
Secondary
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: Month 6 and 12, 60, last observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during core study were included in the ITT population. The n number of patients with T2 and T1 information recorded at scan
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 60 (Extension) n=45, 49, 43 | 88.9 percentage of paticipants |
| Placebo | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 6 (Core), n= 80, 87, 83 | 47.5 percentage of paticipants |
| Placebo | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Last observation (Extension) n=92, 93,90 | 72.8 percentage of paticipants |
| Placebo | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 12 (Extension) n=70, 77, 70 | 57.1 percentage of paticipants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 60 (Extension) n=45, 49, 43 | 87.8 percentage of paticipants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 12 (Extension) n=70, 77, 70 | 67.5 percentage of paticipants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 6 (Core), n= 80, 87, 83 | 77.0 percentage of paticipants |
| Fingolimod (FTY720) 1.25 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Last observation (Extension) n=92, 93,90 | 76.3 percentage of paticipants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Last observation (Extension) n=92, 93,90 | 78.9 percentage of paticipants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 6 (Core), n= 80, 87, 83 | 80.7 percentage of paticipants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 12 (Extension) n=70, 77, 70 | 72.9 percentage of paticipants |
| Fingolimod (FTY720) 5.0 mg/Day | Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit | Month 60 (Extension) n=45, 49, 43 | 83.7 percentage of paticipants |
Secondary
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
The Expanded Disability Status Scale (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. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: Month 6,12,60 and Last observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. A patient at risk are those continuing in the study without an event before the specified timepoint The n denotes number of patients at risk.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2400 days (n=21, 26, 27) | 0.46 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 0 days (n=93,94,94) | 1.00 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 200 days (n=57, 73, 70) | 0.69 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 400 days (n=48, 63, 60) | 0.62 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 600 days (n=41, 57, 52) | 0.58 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 800 days (n=38, 48, 48) | 0.55 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1000 days (n=35, 42, 45) | 0.53 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1200 days (n=30, 38 40) | 0.51 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1400 days (n=29, 36, 35) | 0.51 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1600 days (n=27, 34, 34) | 0.51 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1800 days (n=25, 33, 33) | 0.51 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2000 days (n=23, 31, 31) | 0.51 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2200 days (n=22, 28, 30) | 0.49 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2600 days (n=9, 12, 12) | 0.44 percentage of participants |
| Placebo | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2880 days (n=0, 0, 0) | 0 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2400 days (n=21, 26, 27) | 0.55 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1400 days (n=29, 36, 35) | 0.63 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 0 days (n=93,94,94) | 1.00 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1200 days (n=30, 38 40) | 0.66 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2000 days (n=23, 31, 31) | 0.59 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 200 days (n=57, 73, 70) | 0.86 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2880 days (n=0, 0, 0) | 0 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1600 days (n=27, 34, 34) | 0.61 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 400 days (n=48, 63, 60) | 0.78 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1000 days (n=35, 42, 45) | 0.70 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2600 days (n=9, 12, 12) | 0.55 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 600 days (n=41, 57, 52) | 0.76 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1800 days (n=25, 33, 33) | 0.61 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2200 days (n=22, 28, 30) | 0.55 percentage of participants |
| Fingolimod (FTY720) 1.25 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 800 days (n=38, 48, 48) | 0.75 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1800 days (n=25, 33, 33) | 0.68 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2200 days (n=22, 28, 30) | 0.66 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1000 days (n=35, 42, 45) | 0.75 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1200 days (n=30, 38 40) | 0.70 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2400 days (n=21, 26, 27) | 0.66 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1400 days (n=29, 36, 35) | 0.70 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 1600 days (n=27, 34, 34) | 0.68 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 800 days (n=38, 48, 48) | 0.75 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2600 days (n=9, 12, 12) | 0.66 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 0 days (n=93,94,94) | 1.00 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 200 days (n=57, 73, 70) | 0.86 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2000 days (n=23, 31, 31) | 0.66 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 400 days (n=48, 63, 60) | 0.79 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 2880 days (n=0, 0, 0) | 0 percentage of participants |
| Fingolimod (FTY720) 5.0 mg/Day | Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients | 600 days (n=41, 57, 52) | 0.78 percentage of participants |
Secondary
Volume of T2-weighted Lesions
Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Time frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The n in each category indicates participants with T2 information recorded at specific timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Volume of T2-weighted Lesions | Month 12 (Extension) n= 73, 79, 72 | 8264.1 mm^3 | Standard Deviation 10121.43 |
| Placebo | Volume of T2-weighted Lesions | Month 60 (Extension) n=45, 50, 44 | 6698.3 mm^3 | Standard Deviation 9569.98 |
| Placebo | Volume of T2-weighted Lesions | Month 6 (Core) n=85, 91, 87 | 9016.0 mm^3 | Standard Deviation 10361.83 |
| Placebo | Volume of T2-weighted Lesions | Last observation (Extension) n=87, 91, 88 | 8757.2 mm^3 | Standard Deviation 10127.01 |
| Fingolimod (FTY720) 1.25 mg/Day | Volume of T2-weighted Lesions | Month 12 (Extension) n= 73, 79, 72 | 10707.1 mm^3 | Standard Deviation 14887.66 |
| Fingolimod (FTY720) 1.25 mg/Day | Volume of T2-weighted Lesions | Month 6 (Core) n=85, 91, 87 | 10084.6 mm^3 | Standard Deviation 14774.16 |
| Fingolimod (FTY720) 1.25 mg/Day | Volume of T2-weighted Lesions | Month 60 (Extension) n=45, 50, 44 | 9498.7 mm^3 | Standard Deviation 9765.6 |
| Fingolimod (FTY720) 1.25 mg/Day | Volume of T2-weighted Lesions | Last observation (Extension) n=87, 91, 88 | 10090.2 mm^3 | Standard Deviation 13999.5 |
| Fingolimod (FTY720) 5.0 mg/Day | Volume of T2-weighted Lesions | Month 60 (Extension) n=45, 50, 44 | 6626.9 mm^3 | Standard Deviation 9146.01 |
| Fingolimod (FTY720) 5.0 mg/Day | Volume of T2-weighted Lesions | Month 6 (Core) n=85, 91, 87 | 8331.1 mm^3 | Standard Deviation 10162.01 |
| Fingolimod (FTY720) 5.0 mg/Day | Volume of T2-weighted Lesions | Month 12 (Extension) n= 73, 79, 72 | 8363.2 mm^3 | Standard Deviation 10694.82 |
| Fingolimod (FTY720) 5.0 mg/Day | Volume of T2-weighted Lesions | Last observation (Extension) n=87, 91, 88 | 8061.8 mm^3 | Standard Deviation 9003.47 |