A double-blind, randomized, multicenter, placebo controlled, parallel-group study comparing the efficacy and safety of 0.5mg FTY720 administered orally once daily versus placebo in patients with primary progressive multiple sclerosis
This is a randomized, multicenter, double-blind, placebo-controlled, parallel-group study in
approximately 940 patients with PPMS. Patients will be randomized to receive a fixed once
daily dose of 0.5 mg Po. FTY720 or matching placebo. We plan to recruit ten patients at uT Southwestern Medical Center in the Clinical Center for MS.
The study will consist of two Phases: a Pre-Randomization Phase (lasting for up to 45 days) and a Double-blind Treatment Phase which will last until the last patient still ongoing in the study completes the Double-blind Treatment Phase (Month 36, if not discontinued earlier). For the last patient randomized, the Double-blind Treatment Phase will last for a maximum of 3 years. For all other patients the maximum duration will depend on the duration of the enrolment period and the time point of randomized. Faster patient accrual will result in a shorter study duration. Thus, if the target sample size is reached within 18 months of enrollment, the maximum duration of the Double-blind Treatment Phase for the first patient randomized would be 4.5 years. if the observed overall progression rate is slower than assumed, the study may be prolonged to maintain the statistical power for detecting a treatment difference. The maximum duration of the study in any event will not exceed 5 years.
* male or female
* 25 through 65 years of age inclusive
* females of childbearing potential must have a negative pregnancy test at Baseline and use simultaneously two forms of effective contraception during the treatment and 3 months after discontinuation of study medication
* sign written informed consent prior to participating in the study
Primary Progressive Multiple Sclerosis
* diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria):
- one year of disease progression plus
- two of the following: a) positive brain MRI (nine T2 lesions or four or more T2 lesions with positive visual evoked potential), b) positive spinal cord MRI (two focal T2 lesions), c) positive CSF.
* central review of the diagnostic criteria for PPMS will be required for all patients prior to randomization.
* duration of disease at Baseline
- time since first reported symptoms between 2 and 10 years
* documented evidence of clinical disability progression in the 2 years prior to Screening
- clinical disability progression should have been observed in each of the previous 2 years prior to Screening as per clinical judgment of the investigator.
- in addition, disability progression must be documented by an increase in the EDSS score of at least 0.5 points at any time point during the 2 years prior to Screening. Should documented EDSS scores not be available, a written summary of the clinical evidence of disability progression in the previous 2 years must be submitted for central review.
* disability status at Screening
- EDSS score of 3.5-6.0 inclusive
- pyramidal functional system score of 2 or more
- 25[Right Quote]TWT less than 30 seconds