A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
The purpose of the study is to determine if cladribine tablets are a safe and effective
 treatment for relapsing-remitting multiple sclerosis (RRMS).
This is a randomized, double-blind, three-arm, placebo-controlled, multi-center study. The
 study includes a pre-study evaluation period (up to 28 days prior to the start of treatment);
 an initial treatment period from Week 1 to 48; and a re-treatment period during Week 49 to
 96.

 During the initial treatment period (Week 1 to 48), eligible subjects are equally randomized
 by a central randomization system to receive either a) cladribine at a low dose (0.875
 milligram per kilogram per course [mg/kg/course] for two courses plus placebo for two
 courses); b) cladribine at a high dose (0.875 mg/kg/course for four courses); or c) placebo
 (four courses). During the re-treatment period (Weeks 49 to 96), subjects received either a)
 cladribine at a low dose (0.875 mg/kg/course for two courses); or b) placebo (two courses).

 For all randomized subjects, there is a rescue option of treatment with Rebif® (interferon
 beta-1a 44 microgram (mcg) given subcutaneously three times a week), if the subject
 experienced more than one qualifying relapse, and/or experienced a sustained increase in
 their EDSS score of greater than or equal to (>=) 1 point, or >=1.5 points if baseline EDSS
 score is 0, (over a period of three months or greater), during a calendar year beginning at
 Week 24.

 To maintain the blind, there is a treating physician who view clinical laboratory results and
 assess adverse events and safety information, and an independent blinded evaluating physician
 who will perform neurological exams. A central neuroradiology center, also blinded to
 treatment, will assess magnetic resonance imaging (MRI) evaluations.
Inclusion Criteria:

 -  Male or female, between 18 and 65 years of age (inclusive, at time of informed
 consent)

 -  Has definite MS according to the McDonald criteria

 -  Has relapsing-remitting disease with 1 or more relapses within 12 months prior to
 Study Day 1

 -  Must have been clinically stable and not has a relapse within 28 days prior to Study
 Day 1

 -  Has MRI consistent with MS at the pre-study evaluation according to the Fazekas
 criteria

 -  Has a EDSS score from 0 to 5.5, inclusive

 -  Weighed between 40-120 kilogram (kg), inclusive

 -  If female, she must:

 1. be post-menopausal or surgically sterilized; or

 2. uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide,
 or condom with spermicide, for the duration of the study; and

 3. be neither pregnant nor breast-feeding

 -  If male, he must be willing to use contraception to avoid pregnancies

 -  Be willing and able to comply with study procedures for the duration of the study

 -  Voluntarily provides written informed consent, and for United states of America (USA)
 sites only, a subject authorization under Health Insurance Portability and
 Accountability Act (HIPAA)

 Exclusion Criteria:

 -  Has 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 on the basis of efficacy

 -  Has significant leukopenia (white blood cell count less than 0.5 times the lower limit
 of normal of the central laboratory) within 28 days prior to Study Day 1

 -  Has received cladribine, mitoxantrone, total lymphoid irradiation, myelosuppressive
 therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab

 -  Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28
 days prior to Study Day 1

 -  Has compromised immune function or infection

 -  Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28
 days prior to Study Day 1

 -  Has received cytokine-based therapy, intravenous immunoglobulin therapy, or
 plasmapheresis within 3 months prior to Study Day 1

 -  Has platelet and absolute neutrophil counts below the lower limit of normal range
 within 28 days prior to Study Day 1

 -  Has prior or current history of malignancy

 -  Has a history of persistent anemia, leukopenia, neutropenia, or thrombocytopenia after
 immunosuppressive therapy

 -  Has systemic disease that, in the opinion of the Investigator, might interfere with
 subject safety, compliance or evaluation of the condition under Study (for example,
 insulin-dependent diabetes, Lyme disease, clinically significant cardiac, hepatic, or
 renal disease, Human Immunodeficiency Virus, or Human T-Cell Lymphotrophic Virus
 Type-1)

 -  Has a psychiatric disorder that, in the opinion of the Investigator, was unstable or
 would preclude safe participation in the study

 -  Has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients

 -  Has used any investigational drug or experimental procedure within 6 months prior to
 Study Day 1