The purpose of the study is to determine if cladribine is a safe and effective treatment for relapsing-remitting MS

This will be a randomized, double-blind, three-arm, placebo-controlled, multi-center study. The study will include a pre-study evaluation period (up to 28 days prior to the start of treatment); an initial treatment period during Year 1; and a retreatment period during Year 2.

During the initial treatment period in Year 1, eligible subjects will be equally randomised by a central randomisation system to receive either a) cladribine at a low dose (0.875 mg/kg/cycle for two cycles + placebo for two cycles); b) cladribine at a high dose (0.875 mg/kg/cycle for four cycles); or c) placebo (four cycles). During the retreatment period in Year 2, subjects will receive either a) cladribine at a low dose (0.875 mg/kg/cycle for two cycles); or b) placebo (two cycles).

For all randomized subjects, there will be a rescue option of treatment with Rebif (44 mcg three times a week (tiw)) if the subject experiences more than one qualifying relapse, and/or experiences a sustained increase in their EDSS of ³one point, or ³1.5 points if baseline EDSS was 0, (over a period of three months or greater), during a calendar year beginning at Week 24.

To maintain the blind, there will be a Treating Physician who will view clinical laboratory results and assess AEs and safety information, and an independent blinded Evaluating Physician who will perform neurological exams. A central neuroradiology center, also blinded to treatment, will assess MRI evaluations.

Inclusion Criteria:

• 18 -65 years of age
• Definite MS according to the McDonald criteria
• Relapsing-remitting disease with 1 or more relapses within 12 months
• No relapse within 28 days
• MRI consistent with MS
• EDSS from 0-5.5
• Weigh between 40-120 kg
• Males and females must use contraception

Exclusion Criteria:

• Pregnant or breast feeding
• Secondary Progressive MS (SPMS) or Primary Progressive MS (PPMS)
• Prior use of disease modifying drugs (DMDs) within the last 3 months, or 2 or more prior treatment failures with DMDs
• Compromised immune function or infection, or prior use of medications that altered the immune system
• Significant clinical or laboratory abnormalities at the screening visit (abnormal platelet, neutrophil or white blood cell counts)
• Prior or current history of malignancy
• History of blood disorders after immunosuppressive therapy
• Systemic disease or psychiatric disorder that might interfere with subject safety, compliance or evaluation of MS
• Use of any investigational drug or experimental procedure within 6 months