A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Ocrelizumab; Ocrelizumab
Intervention description: Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).; Participants will receive an additional single 600-mg dose IV infusion at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Intervention MeSH terms: Ocrelizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 608.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of ocrelizumab in participants with RRMS who
      have had a suboptimal response to an adequate course of DMT. Participants will receive
      ocrelizumab as an initial dose of two 300-milligrams (mg) intravenous (IV) infusions (600 mg
      total) separated by 14 days followed by one 600-mg IV infusion for a maximum of 4 doses (up
      to 96 weeks). Anticipated time on study treatment is 96 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of multiple sclerosis (specifically RRMS), in accordance with the revised
             2010 McDonald criteria

          -  Disease duration from first symptom of less than or equal to (</=) 12 years

          -  Treated with an adequate course of treatment with no more than three prior DMT
             regimens of greater than or equal to (>/=) 6 months, and the discontinuation of the
             most recent adequately used DMT was due to suboptimal response

          -  Suboptimal response while the participant was on his/her last adequately used DMT for
             >/=6 months (defined by having one of the following qualifying events despite being on
             a stable dose of the same DMT for at least 6 months: one or more clinically reported
             relapses, one or more T1 Gd-enhanced lesions, or two or more new or enlarging T2
             lesions on MRI); these qualifying events must have occurred while on the last
             adequately used DMT. In participants receiving stable doses of the same approved DMT
             for more than a year, the event must have occurred within the last 12 months of
             treatment with this DMT from the date of screening

        Exclusion Criteria:

          -  History of primary progressive multiple sclerosis (PPMS), progressive relapsing
             multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)

          -  Contraindications for MRI

          -  Known presence of other neurological disorders that may mimic multiple sclerosis

          -  Pregnancy or lactation, or intention to become pregnant during the study

          -  Requirement for chronic treatment with systemic corticosteroids or immunosuppressants
             during the course of the study

          -  History of or currently active primary or secondary immunodeficiency

          -  Lack of peripheral venous access

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies

          -  Active infection, or history of or known presence of recurrent or chronic infection
             such as human immunodeficiency virus (HIV), syphilis, or tuberculosis

          -  History of progressive multifocal leukoencephalopathy

          -  Contraindications to or intolerance of oral or IV corticosteroids

          -  Previous treatment with fingolimod (Gilenya®) or dimethyl fumarate (Tecfidera®) in
             participants whose lymphocyte count is below the lower limit of normal (LLN)

          -  Treatment with alemtuzumab (Lemtrada®)

          -  Previous treatment with systemic cyclophosphamide, azathioprine, mycophenolate
             mofetil, cyclosporine, or methotrexate

          -  Previous treatment with natalizumab within 12 months prior to screening unless failure
             was due to confirmed, persistent anti-drug antibodies (ADAs). Participants previously
             treated with natalizumab will be eligible for this study only if duration of treatment
             with natalizumab was less than (<) 1 year and natalizumab was not used in the 12
             months prior to screening. Anti-John Cunningham virus (JCV) antibody status (positive
             or negative) and titer (both assessed within the year of screening) must be documented
             prior to enrollment

          -  Treatment with dalfampridine (Ampyra®) unless on stable dose for >/=30 days prior to
             screening

          -  Treatment with a B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept,
             belimumab, or ofatumumab)

          -  Treatment with a drug that is experimental (Exception: treatment with an experimental
             drug that was subsequently approved in the participant's country is allowed)