Multiple Sclerosis
Conditions
Keywords
FTY720,, MS
Brief summary
To provide efficacy and safety data of two doses (0.5 mg and 1.25 mg) of FTY720 in Japanese patients with relapsing multiple sclerosis (MS)
Interventions
DRUGFTY720
Administered orally once daily for 6 months
DRUGPlacebo
Administered orally once daily for 6 months
Sponsors
Tanabe Pharma Corporation
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients aged 18-60 * Patients with a diagnosis of multiple sclerosis
Exclusion criteria
* Patients with a history or presence of chronic disease of the immune system other than MS * Patients with a history or presence of malignancy, pulmonary or heart disease, etc. * Pregnant or nursing (lactating) women Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6 | Month 3 and Month 6 | Brain Magnetic Resonance Imaging (MRI) was performed at Month 3 and Month 6. Gadolinium-enhancing lesions (active lesions) represent acute inflammatory activity only and dissipate within 2-8 weeks of appearance. MRI scans were analyzed by blinded readers at the central MRI Evaluation Center to ensure consistency. Any Gd-enhanced T1 weighted MRI data obtained less than 14 days after the steroid used to treat MS relapses is invalid and excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only) | up to Month 6 | A relapse must have been confirmed by a neurologist and 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). |
| Number of Patients Free of New or Newly Enlarged T2 Lesions | up to Month 3 and up to Month 6 | The number of T2 lesions were obtained from MRI scans at Screening visit. The numbers of new/newly enlarging T2 lesions were obtained from MRI scans at Month 3 or more. New lesions were identified by comparing each lesion already seen in previous examinations. Lesions expanding throughout several slices were counted as only one lesion. |
| Annualized Relapse Rate (ARR) at 6 Months | 6 Months | Annualized relapse rate (ARR) of the treatment group is calculated by taking the total number of confirmed relapses for all the patients in the treatment group divided by the total number of days on study for all patients in the group and multiplied by 365.25 to obtain the annual rate. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FTY720 1.25 mg Administered orally once daily for 6 months | 57 |
| FTY720 0.5 mg Administered orally once daily for 6 months | 57 |
| Placebo Administered orally once daily for 6 months | 57 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 | 3 |
| Overall Study | Discontinued before initiating treatment | 3 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | FTY720 1.25 mg | FTY720 0.5 mg | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 36.0 years STANDARD_DEVIATION 9.31 | 35.0 years STANDARD_DEVIATION 9.01 | 35.0 years STANDARD_DEVIATION 8.93 | 35.3 years STANDARD_DEVIATION 9.04 |
| Region of Enrollment Japan | 57 participants | 57 participants | 57 participants | 171 participants |
| Sex: Female, Male Female | 39 Participants | 40 Participants | 39 Participants | 118 Participants |
| Sex: Female, Male Male | 18 Participants | 17 Participants | 18 Participants | 53 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 | 42 / 54 | 41 / 57 | 27 / 57 |
| serious Total, serious adverse events | 11 / 54 | 5 / 57 | 3 / 57 |
Outcome results
Primary
Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6
Brain Magnetic Resonance Imaging (MRI) was performed at Month 3 and Month 6. Gadolinium-enhancing lesions (active lesions) represent acute inflammatory activity only and dissipate within 2-8 weeks of appearance. MRI scans were analyzed by blinded readers at the central MRI Evaluation Center to ensure consistency. Any Gd-enhanced T1 weighted MRI data obtained less than 14 days after the steroid used to treat MS relapses is invalid and excluded.
Time frame: Month 3 and Month 6
Population: Modified Full Analysis Set (Modified FAS) included all patients who were randomized and received at least one dose of study drug and had at least one valid post-randomized MRI scan at Month 3 or longer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTY720 1.25 mg | Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6 | 43 Participants |
| FTY720 0.5 mg | Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6 | 35 Participants |
| Placebo | Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6 | 21 Participants |
Secondary
Annualized Relapse Rate (ARR) at 6 Months
Annualized relapse rate (ARR) of the treatment group is calculated by taking the total number of confirmed relapses for all the patients in the treatment group divided by the total number of days on study for all patients in the group and multiplied by 365.25 to obtain the annual rate.
Time frame: 6 Months
Population: Full Analysis Set (FAS) consisted of all patients who were randomized and received at least one dose of study drug. This population was only used for the analyses of relapse and EDSS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTY720 1.25 mg | Annualized Relapse Rate (ARR) at 6 Months | 0.407 Relapses per year |
| FTY720 0.5 mg | Annualized Relapse Rate (ARR) at 6 Months | 0.512 Relapses per year |
| Placebo | Annualized Relapse Rate (ARR) at 6 Months | 1.131 Relapses per year |
Secondary
Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only)
A relapse must have been confirmed by a neurologist and 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).
Time frame: up to Month 6
Population: Full Analysis Set (FAS) consisted of all patients who were randomized and received at least one dose of study drug. This population was only used for the analyses of relapse and EDSS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTY720 1.25 mg | Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only) | 45 Participants |
| FTY720 0.5 mg | Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only) | 45 Participants |
| Placebo | Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only) | 37 Participants |
Secondary
Number of Patients Free of New or Newly Enlarged T2 Lesions
The number of T2 lesions were obtained from MRI scans at Screening visit. The numbers of new/newly enlarging T2 lesions were obtained from MRI scans at Month 3 or more. New lesions were identified by comparing each lesion already seen in previous examinations. Lesions expanding throughout several slices were counted as only one lesion.
Time frame: up to Month 3 and up to Month 6
Population: Modified Full Analysis Set (Modified FAS) included all patients who were randomized and received at least one dose of study drug and had at least one valid post-randomized MRI scan at Month 3 or longer.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FTY720 1.25 mg | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 3 (n = 50, 49, 51) | 30 Participants |
| FTY720 1.25 mg | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 6 (n = 48, 48, 50) | 28 Participants |
| FTY720 0.5 mg | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 3 (n = 50, 49, 51) | 34 Participants |
| FTY720 0.5 mg | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 6 (n = 48, 48, 50) | 31 Participants |
| Placebo | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 3 (n = 50, 49, 51) | 23 Participants |
| Placebo | Number of Patients Free of New or Newly Enlarged T2 Lesions | Month 6 (n = 48, 48, 50) | 18 Participants |