• To evaluate the safety and tolerability of FTY720 compared to placebo in patients with PPMS [ Time Frame: when the last patient still ongoing in the study completes Month 36 of the double blind treatment phase ] [ Designated as safety issue: Yes ]
• To evaluate the effect of FTY720 relative to placebo on conventional MRI parameters [ Time Frame: When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study ] [ Designated as safety issue: No ]
• To evaluate the effect of FTY720 relative to placebo on Patient Reported Outcomes [ Time Frame: When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study ] [ Designated as safety issue: No ]

• To evaluate the safety and tolerability of FTY720 compared to placebo in patients with PPMS
• To evaluate the effect of FTY720 relative to placebo on conventional MRI parameters
• To evaluate the effect of FTY720 relative to placebo on Patient Reported Outcomes

The purpose of this study is to evaluate whether FTY720 is effective in delaying MS disability progression compared to placebo in patients with PPMS.

• Drug: Placebo
• Drug: FTY720D 1.25mg

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.