The primary objective of this study is to assess the efficacy of Ocrelizumab (OCR) in Relapsing Multiple Sclerosis patients who have been previously treated with natalizumab (NTZ) by evaluating relapse rate, progression on MRI and disability progression.

This is a multicenter, prospective, open-label, Phase IV clinical trial. Patients with relapsing forms of Multiple Sclerosis (MS), ages 18 to 65, who have received a stable dose of NTZ for 12 or more consecutive months, and have been free of relapses, disability worsening or Magnetic Resonance Imaging (MRI) progression 6 months prior to the transition screening visit will be eligible for the study. After informed consent to participate has been obtained, the patient will have physical exam (PE), non-blinded Expanded Disability Status Scale (EDSS), MRI, Multiple Sclerosis Impact Scale (MSIS-29) and labs done for the screening visit to determine eligibility. Brain MRI with and without contrast will be performed with the standard MS protocol. MRIs will be performed with 3mm slice thickness with no gaps between slices. Patients will receive their first dose of OCR 4 to 6 weeks after the last dose of NTZ. Other baseline measures, including physical exam, EDSS, MSIS-29, and labs will be performed within 4 weeks of screening. Physical exam, non-blinded EDSS, and labs will be performed at month 3, month 6, month 9, and month 12. MSIS-29 will be performed at months 6 and 12. In addition, MRIs will be performed at months 3, 6, and 12.

Inclusion Criteria:

• Male or female with relapsing form of MS, age 18 to 65, inclusive, at the time of informed consent.
• In the opinion of the investigator, able to understand the purpose and risk of the study and provide signed informed consent document.
• Must have received a stable dose of NTZ for 12 or more consecutive months, and have had no evidence of on-NTZ disease activity (clinically or on MRI) for the 6 months prior to the screening visit.
• Naïve to OCR.
• No evidence, in the opinion of the investigators of significant cognitive limitation or psychiatric disorder that would interfere with the conduct of the study.
• EDSS of ≤ 6.0 at screening.
• Female patients of childbearing potential must practice effective contraception and continue contraception during the study.

Exclusion Criteria:

• History of primary or secondary progressive multiple sclerosis.
• Evidence of active hepatitis B infection at screening.
• Any mental condition of such that patient is unable to understand the nature, scope, and possible consequences of the study.
• Patients with untreated hepatitis C or tuberculosis. Patients who have history of progressive multifocal leukoencephalopathy (PML) or known to be HIV positive, per standard care.
• Any persistent or severe infection.
• Pregnancy or lactation.
• Significant or uncontrolled somatic disease or severe depression in the last year.
• Inability to complete an MRI.
• Previous treatment with B-cell targeted therapies.
• Current use of immunosuppressive medication.
• Patients who have had evidence of disease activity within the 6 months prior to screening. This includes MS relapse, or new or enlarging T2 lesions or Gd+ enhancing lesions, or disability progression.
• Patients with any significant comorbidity that in the opinion of the investigator, would interfere with participation in the study.

Male and female patients with relapsing forms of MS, ages 18 to 65, must have received a stable dose of NTZ for 12 or more consecutive months, and have been free of relapses, disability worsening or MRI progression 6 months prior to switching from NTZ to OCR therapy are eligible to participate.

12 months