A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

A Phase III, Randomized, Double-blind, Three-arm, Placebo-controlled, Multi-center Study to Evaluate the Safety and Efficacy 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