Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies

Key Inclusion Criteria: * Subjects of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study. * Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria \[Polman 2011\]) at Screening. * Must have been treated with Gilenya or Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera (BRACET) for at least the 12 months prior to Screening with no interruption of treatment greater than 1 month. Prior treatment with natalizumab is allowed; however, there must be a minimum 1 year since last natalizumab infusion and the Screening visit of this study, and if discontinuation of natalizumab in the past was not due to intolerance, anti-natalizumab antibodies, or efficacy loss. * Must have had disease activity in the 6 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 gadolinium enhancing lesion OR at least 2 new T2 lesions compared with magnetic resonance imaging done within 12 months of screening OR clinical relapse, or Expanded Disability Status Scale \[EDSS\] progression of 1 point) * Must have an EDSS score from 0 to 5.5 inclusive at Screening. * Must have lymphocyte count that is documented as at or above the lower limit of normal (LLN) by the day before the first Tysabri infusion. If lymphocytes have not returned to LLN or above the day before the first Tysabri infusion (day 0), the subject has screen failed. The subject who screen fails is eligible to undergo Rescreening once; if additional Rescreening is considered, please contact the study medical monitor. Key Exclusion Criteria: * History or positive test result at Screening for human immunodeficiency virus. * History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen and/or hepatitis core antibody). * Prior treatment with natalizumab (either commercially or through a clinical study) within 1 year of Day -1. * Contraindications to treatment with natalizumab as described in the Prescribing Information for each of the participating countries. * Known allergy to natalizumab or any of its ingredients, or known to be anti-natalizumab antibody positive. * Diagnosis of primary progressive MS, secondary progressive MS, and/or progressive-relapsing MS. * An MS relapse that has occurred within the 30 days prior to Day -1 and/or the subject has not stabilized from a previous relapse prior to Day -1. * Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible). * History of severe opportunistic infections (including progressive multifocal leukoencephalopathy) or any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator * Clinically severe active infection within 1 month prior to Screening. * Females breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception; women who have a positive pregnancy test result at Day -1. * Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12 months prior to Screening. Prior history of alemtuzumab use at any point in the past. NOTE: Other protocol-defined inclusion/exclusion criteria may apply