A Study to Evaluate the Safety of Administering Ocrelizumab Per a Shorter Infusion Protocol in Participants With Primary Progressive Multiple Sclerosis (PPMS) and Relapsing Multiple Sclerosis (RMS)
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Ocrelizumab Dose 1; Ocrelizumab Dose 2 and Dose 3
Intervention description: 300 mg infusion administered to ocrelizumab-naive participants per approved protocol (over approximately 2.5 hours or longer) as per standard of care followed by a second 300 mg shorter infusion over approximately 1.5 hours.; 600 mg infusion of ocrelizumab administered at a shorter rate (i.e. over the course of approximately 2 hours) at Week 24 and at Week 48
Intervention MeSH terms: Ocrelizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 141.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This study is an open-label, non-randomized study to evaluate rate and severity of
      infusion-related reactions (IRRs) of ocrelizumab infused over a shorter time period than the
      approved administration rate in participants with PPMS or RMS in the United States (U.S.).
      Participants will be enrolled into two cohorts. Cohort 1 will examine the effect of
      administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. This cohort
      will consist of patients who have already received one or two doses of ocrelizumab according
      to the approved infusion protocol (i.e., per the currently U.S. label) and have reported no
      serious IRRs and who will then receive the next infusion of ocrelizumab at a higher rate in
      order to deliver 600 mg over the course of approximately 2 hours. Cohort 2 will examine the
      effect of administering ocrelizumab per a shorter infusion protocol for the second infusion
      of Dose 1. This cohort will consist of ocrelizumab naïve patients who, after receiving
      Infusion 1/Dose 1 of ocrelizumab at the approved rate (300 mg over approximately 2.5 hours or
      longer) have no reported serious IRRs, will then receive the second 300-mg shorter infusion
      over approximately 1.5 hours.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eligible to receive ocrelizumab per the United States Package Insert (USPI)

          -  Able to comply with the study protocol, in the investigator's judgment

          -  Age 18-55 years, inclusive

          -  Have a diagnosis of PPMS or RMS, confirmed per the revised 2017 McDonald criteria

          -  Expanded Disability Status Scale (EDSS) score of 0 to 6.5, inclusive

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of <1% per year during the treatment period and for at least 6 months after the last
             dose of study treatment (per the USPI)

        Exclusion Criteria:

          -  Experienced serious IRR(s)

          -  History of life-threatening infusion reaction to ocrelizumab

          -  Known presence of other neurological disorders

          -  Pregnancy or lactation, or intention to become pregnant during the study

          -  Any concomitant disease that may require chronic treatment with systemic
             corticosteroids or immunosuppressants during the course of the study

          -  Significant, uncontrolled disease, such as cardiovascular (including cardiac
             arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic,
             endocrine, and gastrointestinal or any other significant disease that may preclude
             patient from participating in the study

          -  Congestive heart failure

          -  Known active bacterial, viral, fungal, mycobacterial infection or other infection or
             any severe episode of infection requiring hospitalization or treatment with IV
             antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks
             prior to baseline visit

          -  History of or currently active primary or secondary immunodeficiency

          -  History or known presence of recurrent or chronic infection (e.g., HIV, syphilis,
             tuberculosis)

          -  History of recurrent aspiration pneumonia requiring antibiotic therapy

          -  History of malignancy, including solid tumors and hematological malignancies,except
             basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the
             cervix of the uterus that have been excised with clear margins

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies

          -  History of alcohol or drug abuse within 24 weeks prior to enrollment

          -  Receipt of a live vaccine within 6 weeks prior to enrollment

          -  Systemic corticosteroid therapy within 4 weeks prior to enrollment

          -  Contraindications to or intolerance of oral or IV corticosteroids, including IV
             methylprednisolone (or equivalent steroid) administered according to the country label

          -  Treatment with alemtuzumab

          -  Treatment with a B-cell targeted therapies other than ocrelizumab

          -  Treatment with a drug that is experimental

          -  Abnormal laboratory results per local laboratory standards and investigator assessment