FTY720 in Patients With Primary Progressive Multiple Sclerosis (INFORMS)

Inclusion Criteria:

General

1. sign written informed consent prior to participating in the study
2. 25 through 65 years of age inclusive

3. females of childbearing potential must:

   • have a negative pregnancy test at Baseline (prior to randomization) and
   • use simultaneously two forms of effective contraception during the treatment and 3-months after discontinuation of study medication

Primary Progressive Multiple sclerosis.

1. diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria):
2. time since first reported symptoms between 2 and 10 years
3. evidence of clinical disability progression in the 2 years prior to Screening

4. disability status at Screening

   • EDSS score of 3.5-6.0 inclusive
   • pyramidal functional system score of 2 or more
   • 25'TWT less than 30 seconds

Exclusion Criteria:

PPMS specific:

• History of relapses/attacks
• Progressive neurological disorder other than PPMS
• Pure cerebellar syndrome or pure visual progressive syndrome or pure
• cognitive progressive syndrome
• Presence of spinal cord compression at screening MRI
• Relevant history of vitamin B12 deficit
• Evidence of syphilis or borreliosis at Screening

Cardiovascular conditions:

• Myocardial infarction within the past 6 months or current unstable ischemic heart disease
• History of angina pectoris due to coronary spasm or history of Raynaud's phenomenon
• Severe cardiac failure or cardiac arrest
• History of symptomatic bradycardia
• Resting pulse <55 bpm pre-dose
• History of sick sinus syndrome or sino-atrial heart block
• History or presence of second and third degree AV block or an increase QT interval (QTc>440 ms)
• Arrythmia requiring treatment with class III antiarrythmic drugs
• History of positive tilt test from workout of vasovagal syncope
• Hypertension, not controlled with medication

Pulmonary:

• Severe respiratory disease or pulmonary fibrosis
• TB
• Abnormal X-ray, suggestive of active pulmonary disease
• Abnormal PFT: <70% of predicted for FEV1 and FVC; <60% for DLCO
• Patients receiving chronic (daily) therapies for asthma

Hepatic:

• Known history of alcohol abuse, chronic liver or biliary disease
• Total or conjugated Brb >ULN, unless in context of Gilbert's syndrome
• AP >1.5xULN; ALT/AST >2xULN; GGT>3xULN

Other:

• History of chronic disease of the immune system other than MS
• Malignancy (other than successfully treated SCC or BCC)
• Diabetes Mellitus
• Macular Edema present at screening
• HIV, Hepatitis C or B, other active infection
• History of total lymphoid irradiation or bone marrow transplantation
• Serum creatinine >1.7 mg/dl
• WBC <3500 cells/mm3
• Lymphocyte count <800 cells/mm3
• History of substance abuse or any other factor that may interfere with subject ability to cooperate and comply with the study procedures
• Unable to undergo MRI scans
• Participation in any therapeutical clinical research study in the 6 months prior to randomization
• Pregnant or lactating women

• Drugs requiring wash-out period:

  3 months:

  • Systemic corticosteroids or ACTH

  • INF-beta

    6 months:

  • Immunosuppressive medication
  • Immunoglobulins
  • Monoclonal antibodies
• Drugs that exclude participation in the study:
• Cladribine
• Cyclophosphamide
• Mitoxantrone (except: patients who received a cumulative dose of no more than 60mg/m2 more than 5 years ago could enter the study)

Other protocol-defined inclusion/exclusion criteria may apply.