Inclusion Criteria:
Patients who meet the following inclusion criteria will be eligible for enrollment in the study:
1. Age between 18 and 60 years, inclusive.
2. Diagnosis of relapsing forms of MS, to include RRMS and active SPMS, diagnosed with McDonald Criteria 2005, 2010, and/or 2017 (1-3)
3. EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
4. Has had a minimum of 12 months of continuous natalizumab therapy (300 mg/d), including patients receiving extended interval dosing of natalizumab (e.g., less frequently than every-4-week infusion).
5. Negative history for any relapses at least 28 days prior to enrollment.
6. Weighing between 40 kilograms or more.
7. Female subjects of childbearing potential must use effective methods of contraception to prevent pregnancy for 4 weeks before initiation of cladribine tablets and must agree to continue to practice adequate contraception for at least 6 months after the last dose. Women using systemically acting hormonal contraceptives should add a barrier method during cladribine treatment and for at least 4 weeks after the last dose in each treatment year.
8. Female subjects must not be pregnant; female subjects must not be lactating or breast-feeding at least 10 days after the last dose.
9. Male subjects must be willing to use a condom during dosing and for six months after the last dose. Alternatively, their female partner must use another form of contraception (such as an intra-uterine device \[IUD\], barrier method with spermicide, or hormonal contraceptive \[e.g., implant, injectable, patch or oral\]) during dosing and for six months after last dose.
10. Understands and is capable of following through with study protocol requirements and assessments.
11. Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA).
Exclusion Criteria:
Patients who meet any of the following exclusion criteria will not be eligible for enrollment in the study:
1. Natalizumab failure based on clinician's discretion.
2. Not active progressive MS (4).
3. A diagnosis of PML or any suspicion of PML.
4. A diagnosis of Clinically Isolated Syndrome
5. Known hypersensitivity to cladribine.
6. Any prior exposure to cladribine.
7. Lymphocyte count not within normal limits of the local, hospital laboratory.
8. Previous or current exposure to mitoxantrone, azathioprine, methotrexate, cyclophosphamide, myelosuppressive treatments, total lymphoid irradiation.
9. Receiving oral or systemic corticosteroid treatments within the 28 days prior to enrollment.
10. Receiving cytokine base treatment, Intra Venous Immuno Globulin (IVIG) or Plasma pheresis, 3 months prior to enrollment in the study.
11. Having platelet count or neutrophil count below the lower limit of the normal range within the 28 days prior to enrollment in the study.
12. Positive for HIV, or positive hepatitis C antibody test or hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM.
13. History of tuberculosis (TB), presence of active tuberculosis, or latent tuberculosis as detected by local standard of practice like imaging (e.g., chest X-ray, chest CT scan, MRI) and/or positive QuantiFERON-TB Gold test and/or skin test and/or clinical examination or has had latent TB disease at any time in the past.
14. Immunocompromised subjects, including subjects currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids.
15. Active malignancy or history of malignancy.
16. Received a live vaccine within 6 weeks prior to cladribine tablet administration or intends to receive a live vaccination during the trial. After the last dose of cladribine tablets, the subject should avoid live vaccine as long as the subject's white blood cell counts are not within normal limits.
17. Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform an MRI.
18. Has any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR \< 30 mL/min/1.73m2)
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