A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Cladribine 5.25 mg/kg; Cladribine 3.5 mg/kg; Placebo
Intervention description: Cladribine tablet will be administered as cumulative dose of 0.875 milligram per kilogram (mg/kg) over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the treatment period of 96 weeks.; Cladribine tablet will be administered as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 48, and 52 and placebo matched to cladribine tablet will be administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.; Placebo matched to cladribine tablet will be administered over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 9, 13, 48 and 52 during the treatment period of 96 weeks.
Intervention MeSH terms: Cladribine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1326.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to determine if cladribine tablets are a safe and effective
      treatment for relapsing-remitting multiple sclerosis (RRMS).
    

Eligibility criteria:

        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