<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02980042</url>
  </required_header>
  <id_info>
    <org_study_id>16-1354</org_study_id>
    <nct_id>NCT02980042</nct_id>
  </id_info>
  <brief_title>Safety of Switching From Rituximab to Ocrelizumab in MS Patients</brief_title>
  <official_title>Evaluating the Tolerability and Safety Profile of Switching From Rituximab to Ocrelizumab: A Real World Evaluation of Patients With Relapsing Forms of Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective between and within group observational study to determine differences&#xD;
      in tolerability, immunogenicity and safety related outcomes for 100 multiple sclerosis (MS)&#xD;
      patients who have been administered at least two infusions of rituximab, six months apart and&#xD;
      are willing to be switched to ocrelizumab compared to a 100 patients who are continuing on&#xD;
      rituximab as a comparison cohort from the clinic population treated as part of clinical care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Studies of rituximab, a chimeric monoclonal antibody against CD20 have shown that B-cell&#xD;
      depletion is of clinical beneﬁt as a potential treatment in relapsing forms of multiple&#xD;
      sclerosis (MS).1 Ocrelizumab is a humanized monoclonal antibody that targets CD20 and&#xD;
      selectively depletes CD20 expressing cells, while preserving the capacity for B cell&#xD;
      reconstitution. When compared with rituximab, ocrelizumab is associated with increased&#xD;
      antibody-dependent cell-mediated cytotoxic eﬀects, and reduced complement-dependent cytotoxic&#xD;
      eﬀects in vitro.2 By increasing antibody-dependent cell mediated cytotoxic eﬀects,&#xD;
      ocrelizumab might modulate tissue-dependent mechanisms of pathogenic response more eﬀectively&#xD;
      compared to rituximab. As a humanized molecule, ocrelizumab is expected to be less&#xD;
      immunogenic with repeated infusions and might thus present a more favorable safety profile&#xD;
      when compared to rituximab.2&#xD;
&#xD;
      Despite rituximab's current off label use in the treatment of MS, currently there is only&#xD;
      data available from phase 2 trials. The HERMES group conducted a phase 2, double-blind,&#xD;
      48-week trial involving 104 patients with relapsing forms of MS; 69 patients received 1000 mg&#xD;
      of intravenous rituximab and 35 patients received placebo on days 1 and 15.3 A significantly&#xD;
      higher number of patients in the rituximab group (78.3%) versus the placebo group (40.0%) had&#xD;
      an infusion related reaction (IRR) events within 24 hours after the first infusion. Within 24&#xD;
      hours after the second infusion, fewer patients in the rituximab group (20.3%) than in the&#xD;
      placebo group (40%) had similar events. A majority of the rituximab group with IRR events&#xD;
      (92.6%) were classified as mild to moderate (grade 1 or 2) in severity.&#xD;
&#xD;
      Safety data from the Investigators Brochure on the OPERA I and II phase 3 trials comparing&#xD;
      ocrelizumab to interferon β-1a on relapsing MS patients showed that IRRs were the most common&#xD;
      adverse events experienced by patients treated with 600 mg of ocrelizumab.4 The percentage of&#xD;
      patients experiencing IRRs was higher in the ocrelizumab group (relapsing forms of MS: 34.3%;&#xD;
      primary progressive forms of MS 39.9%) compared with the interferon β-1a (active control)&#xD;
      group who received placebo infusions (relapsing forms of MS: 9.7%; primary progressive forms&#xD;
      of MS: 25.5%). The rate of IRRs was highest during the first infusion or Dose 1 (27.5% on Day&#xD;
      1; 4.71% on Day 15 of Dose 1) and decreased over time (13.7%; 9.6% and 7.8% following Dose 2,&#xD;
      3, and 4 respectively) for the ocrelizumab treated group. Comparatively, interferon β-1a&#xD;
      users experienced 6.5% of IRRs on Day 1, 2.58% on Day 15, &lt; 2.00% after doses 2, 3 and 4&#xD;
      respectively. The reported IRRs were primarily mild-to-moderate in severity (Grades 1 and 2).&#xD;
      Serious IRRs occurred in 0.1% and 1.0% respectively of relapsing and progressive patients and&#xD;
      treated with ocrelizumab.&#xD;
&#xD;
      Clinical data describing the efficacy and tolerability profile of rituximab and ocrelizumab&#xD;
      has utilized populations with different prior treatment characteristics. In the phase 2&#xD;
      HERMES trials, a majority (78.5%) of rituximab patients had been previously been treated with&#xD;
      a disease modifying therapy in the last 2 years.3 In contrast, the OPERA I and II phase 3&#xD;
      clinical trials, a majority of ocrelizumab patients (72.9% in OPERA I and 73.8% in OPERA II)&#xD;
      represented a treatment naïve population.4 Examining IRRs in patients who have switched from&#xD;
      rituximab to ocrelizumab versus those continuing on rituximab will examine the magnitude of&#xD;
      the IRRs and subsequent tolerability of ocrelizumab in a real world population.&#xD;
&#xD;
      Earlier concepts of MS disease pathology have suggested that pathogenic T cells are&#xD;
      sufficient for the full expression of MS. However, it is now evident that full autoimmune B&#xD;
      cells and humoral immune mechanisms also play key roles. 5 Ocrelizumab is a humanized&#xD;
      monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells. CD20&#xD;
      is a B cell surface molecule that is expressed on pre B cells and mature B cells, but not&#xD;
      expressed earlier in the development of B cells or on mature plasma cells. In all three&#xD;
      ocrelizumab studies (with relapsing and progressive populations), treatment with 600 mg of&#xD;
      ocrelizumab led to rapid and complete depletion of circulating CD19+ B cells within 14 days&#xD;
      post treatment. 4 B cell depletion was sustained throughout treatment period. The median time&#xD;
      to repletion of B cells was 72 weeks (range 27-175 weeks). We hypothesize that in switching&#xD;
      rituximab treated patients to ocrelizumab, the proportion of patients with B cell depletion&#xD;
      (&lt; 1%) 6 months after the first and third infusion of ocrelizumab will be the same as the&#xD;
      baseline assessment which will be 6 months after the last dose of rituximab and similar to&#xD;
      findings in OPERA I and II.&#xD;
&#xD;
      Immunogenicity results from the OPERA I and II trials examined the number of patients who had&#xD;
      treatment induced anti-drug antibodies (ADA) to ocrelizumab. 4 Of the 807 patients who&#xD;
      received ocrelizumab and had an ADA assay from a post baseline sample during the controlled&#xD;
      treatment period, 3 patients (0.4%) showed treatment induced ADA to ocrelizumab. Of these, 1&#xD;
      patient tested positive for neutralizing antibodies (NAB) to ocrelizumab. During the open&#xD;
      label extension phase, the prevalence of ADA continued to remain low with post baseline&#xD;
      incidence of 1.9% (2/103 with treatment induced ADA). Currently there is little evidence&#xD;
      examining the prevalence of treatment induced ADAs to both rituximab and ocrelizumab in&#xD;
      patients that switch from the former to the latter in comparison to continuing rituximab&#xD;
      patients. Therefore, we will perform assays to detect ADAs to both rituximab and ocrelizumab&#xD;
      in all patients switching from rituximab to ocrelizumab at Day 1, 6 months and 12 months on&#xD;
      ocrelizumab.&#xD;
&#xD;
      Finally, IRRs have been hypothesized to be a reaction by autoantibodies to the treatment drug&#xD;
      or possibly from the release of cytokines from CD20 expressing cells as they are destroyed by&#xD;
      ocrelizumab causing a &quot;cytokine storm&quot;. Understanding this process may lead to mechanisms&#xD;
      that may aid in ameliorating these infusion reactions. If they are associated with ADA, then&#xD;
      it might be possible to predictively premedicate these patients only. Alternatively, if they&#xD;
      are associated with cytokine release, it may be possible to eliminate premedication in&#xD;
      patients who are already CD20+cell depleted in subsequent infusions. Therefore, we will assay&#xD;
      the profile of certain cytokines in the serum 4 hours after start of ocrelizumab infusion.&#xD;
&#xD;
      With ocrelizumab expected to enter the MS therapeutic market within the next year, we expect&#xD;
      third party payers within and outside the US will require that the FDA or EMA approved&#xD;
      versions of anti-CD20 monoclonal antibodies be used in the treatment of MS, namely&#xD;
      ocrelizumab. Currently, we estimate several thousand MS patients in the US and Sweden are&#xD;
      taking rituximab currently. Thus, it will be important to demonstrate that switching from a&#xD;
      chimeric anti-CD20 to a fully humanized anti-CD20 does not lead to unexpected infusion&#xD;
      reactions and does not increase the probability of development of anti-drug antibodies.&#xD;
&#xD;
      The Rocky Mountain MS Center (RMMSC) at the University of Colorado Anschutz Medical Campus&#xD;
      prescribed rituximab infusions for 533 MS patients in the last 12 months, of which 323&#xD;
      patients received their infusion at the University of Colorado Hospital's Outpatient Infusion&#xD;
      Center between September, 2015-March, 2016. The RMMSC is one of the few sites nationwide with&#xD;
      large numbers of MS patients treated with rituximab. With the anticipated approval of&#xD;
      ocrelizumab, current rituximab users are being counselled by their MS providers at RMMSC to&#xD;
      consider switching to ocrelizumab post approval, particularly if US Payers adopt the FDA&#xD;
      approved version as the preferred anti-CD20 agent for MS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">March 6, 2019</completion_date>
  <primary_completion_date type="Actual">March 6, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Infusions With &gt;= 1 IRR Between the Switching and Comparator Groups</measure>
    <time_frame>Day 1, Day 15, Week 24</time_frame>
    <description>The investigators will report the proportion of infusions with &gt;= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group.</measure>
    <time_frame>Pre-study (Enrollment), Day 1, Day 15, Week 24</time_frame>
    <description>The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</measure>
    <time_frame>Day 1, pre-study infusions</time_frame>
    <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</measure>
    <time_frame>Day 15, pre-study infusions</time_frame>
    <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</measure>
    <time_frame>Week 24, pre-study infusions</time_frame>
    <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions</measure>
    <time_frame>Day 1, Day 15, Week 24</time_frame>
    <description>We will also compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of Ocrelizumab Anti-drug Anti-bodies</measure>
    <time_frame>Day 1 and Week 24</time_frame>
    <description>Proportion of ocrelizumab patients who test positive for ocrelizumab anti-drug anti-bodies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Rituximab Anti-drug Anti-bodies</measure>
    <time_frame>Day 1 and Week 24</time_frame>
    <description>Proportion of patients who test positive for rituximab anti-drug anti-bodies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>B Cell Depletion (CD19)</measure>
    <time_frame>Day 1, Week 24, 1 Year</time_frame>
    <description>Proportion of patients with CD19% &lt;= 1%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>B Cell Depletion (CD20)</measure>
    <time_frame>Day 1, Week 24, 1 Year</time_frame>
    <description>Proportion of patients with CD20% &lt;= 1%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: Eotaxin - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing Eotaxin concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IFN-gamma - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-10 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-16 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-1RA - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-1RA concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-27 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-27 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-6 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-6 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-7 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-8(HA) - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing IL-8(HA) concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MCP-1 - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MDC - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MIP-1alpha - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing MIP-1alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MIP-1beta - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: TARC - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing TARC concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: TNF-alpha - Pre-Post Infusion - Day 1</measure>
    <time_frame>Day 1</time_frame>
    <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: Exotaxin - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing Exotaxin concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IFN-gamma - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-10 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-16 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-1beta - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-7 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: IL-8 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing IL-8 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MCP-1 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MCP-4 - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing MCP-4 concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MDC - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MIP-1beta - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine: TNF-alpha - Pre-Post Infusion - Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Switching Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ocrelizumab</intervention_name>
    <description>A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
    <arm_group_label>Switching Group</arm_group_label>
    <other_name>Ocrevus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>A chimeric monoclonal antibody against CD20.</description>
    <arm_group_label>Comparator Group</arm_group_label>
    <other_name>Rituxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Switching group:&#xD;
&#xD;
          -  Current active patient of RMMSC&#xD;
&#xD;
          -  18-65 years&#xD;
&#xD;
          -  Diagnosis of relapsing forms of MS&#xD;
&#xD;
          -  Completed ≥ two doses of rituximab with the last dose having been administered:&#xD;
&#xD;
               1. Within 12 months of screening and&#xD;
&#xD;
               2. At least 6 months prior to the first planned infusion of study drug&#xD;
&#xD;
          -  Are receiving their current infusions of rituximab at the University of Colorado&#xD;
             Outpatient Infusion Center&#xD;
&#xD;
          -  Have discussed the possibility of switching to ocrelizumab with their MS provider&#xD;
&#xD;
          -  Screened for Hepatitis B and C and TB within 2 years of first dose of ocrelizumab&#xD;
&#xD;
          -  A negative serum pregnancy test must be available for premenopausal women and for&#xD;
             women &lt;12 months after the onset of menopause, unless they have undergone surgical&#xD;
             sterilization.&#xD;
&#xD;
          -  Women of childbearing potential must agree to use a &quot;highly effective&quot;, hormonal form&#xD;
             of contraception or two &quot;effective&quot; forms of non-hormonal contraception. Contraception&#xD;
             must continue for the duration of study treatment and for at least three months after&#xD;
             the last dose of study treatment&#xD;
&#xD;
          -  Are able to complete patient reported outcomes developed as English written scales.&#xD;
&#xD;
          -  Must be able and willing to give meaningful, written informed consent prior to&#xD;
             participation in the trial, in accordance with local regulatory requirements&#xD;
&#xD;
        Comparator group:&#xD;
&#xD;
          -  Current active patient of RMMSC&#xD;
&#xD;
          -  18-65 years&#xD;
&#xD;
          -  Diagnosis of relapsing forms of MS&#xD;
&#xD;
          -  Completed ≥ two doses of rituximab with the last dose having been administered within&#xD;
             12 months of screening as standard of care&#xD;
&#xD;
          -  Are receiving their current infusions of rituximab as standard of care at the&#xD;
             University of Colorado Outpatient Infusion Center and will continue to do so&#xD;
&#xD;
          -  Are willing to be followed for up to two additional rituximab infusions during the&#xD;
             study period as standard of care&#xD;
&#xD;
          -  Must be able and willing to give meaningful, written informed consent prior to&#xD;
             participation in the trial, in accordance with local regulatory requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Both groups:&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Hypersensitivity to trial medications&#xD;
&#xD;
          -  Hepatic Dysfunction (liver enzymes are 5 times greater than normal)&#xD;
&#xD;
          -  History of Congestive Heart Failure&#xD;
&#xD;
          -  Any history of a positive blood assay for Hepatitis B or C&#xD;
&#xD;
          -  Any history of TB or a positive Quantiferon Gold Assay&#xD;
&#xD;
          -  Concurrent use of immunosuppressant medications&#xD;
&#xD;
          -  Any history of immunodeficiency or other medical condition increasing risk of anti-CD&#xD;
             20 therapy.&#xD;
&#xD;
          -  No serious infection at the time of a scheduled study infusion.&#xD;
&#xD;
          -  Any medical, psychiatric or other condition that could result in the patient not being&#xD;
             able to give fully informed consent, or to comply with the protocol requirements as&#xD;
             determined by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Timothy Vollmer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kavita Nair, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Enrique Alvarez, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 9, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <results_first_submitted>November 25, 2019</results_first_submitted>
  <results_first_submitted_qc>January 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 14, 2020</results_first_posted>
  <last_update_submitted>July 1, 2021</last_update_submitted>
  <last_update_submitted_qc>July 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Ocrelizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT02980042/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Switching Group</title>
          <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
        </group>
        <group group_id="P2">
          <title>Comparator Group</title>
          <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
                <participants group_id="P2" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="93">All 100 subjects completed their Week 24 infusion. 7 subjects did not complete the 12 month visit.</participants>
                <participants group_id="P2" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Insurance issues/treatment plan changes</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Switching Group</title>
          <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
        </group>
        <group group_id="B2">
          <title>Comparator Group</title>
          <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="100"/>
            <count group_id="B2" value="100"/>
            <count group_id="B3" value="200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.30" spread="11.01"/>
                    <measurement group_id="B2" value="43.82" spread="9.97"/>
                    <measurement group_id="B3" value="44.56" spread="10.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="143"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Hispanic or Latino</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="89"/>
                    <measurement group_id="B3" value="181"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black/African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="90"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Expanded Disability Status Scale (EDSS)</title>
          <description>The Expanded Disability Status Scale (EDSS) is a tool used to assess disability in multiple sclerosis patients. Scores range from 0 (least disabled) to 10 (most severely disabled) in increments of 0.5.</description>
          <population>EDSS was not collected for the comparator group at baseline. EDSS is only available for the Switching group.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.5" lower_limit="2" upper_limit="6"/>
                    <measurement group_id="B3" value="3.5" lower_limit="2" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Patient Determined Disease Steps (PDDS)</title>
          <description>The Patient Determined Disease Steps (PDDS) is a patient reported measurement tool used to assess level of disability that the patient perceives in multiple sclerosis patients. Scores range from 0 (least perceived disability) to 10 (most severe perceived disability).</description>
          <population>PDDS was not collected for the comparator group. PDDS is only available for the Switching group.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="B3" value="3" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.20" spread="7.91"/>
                    <measurement group_id="B2" value="11.32" spread="7.97"/>
                    <measurement group_id="B3" value="11.26" spread="7.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Years on rituximab</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="100"/>
                    <count group_id="B2" value="100"/>
                    <count group_id="B3" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.38" spread="1.37"/>
                    <measurement group_id="B2" value="2.44" spread="1.45"/>
                    <measurement group_id="B3" value="2.41" spread="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Infusions With &gt;= 1 IRR Between the Switching and Comparator Groups</title>
        <description>The investigators will report the proportion of infusions with &gt;= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.</description>
        <time_frame>Day 1, Day 15, Week 24</time_frame>
        <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. There were a total of 300 infusions in the Switching group and 200 in the Comparator group. Proportion of IRRs are taken out of total number of infusions.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Comparator Group</title>
            <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Infusions With &gt;= 1 IRR Between the Switching and Comparator Groups</title>
          <description>The investigators will report the proportion of infusions with &gt;= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.</description>
          <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. There were a total of 300 infusions in the Switching group and 200 in the Comparator group. Proportion of IRRs are taken out of total number of infusions.</population>
          <units>percentage of infusions with IRRs</units>
          <param>Number</param>
          <units_analyzed>Infusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Infusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="300"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1996</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was necessary because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>.6616</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.3666</ci_lower_limit>
            <ci_upper_limit>1.1942</ci_upper_limit>
            <estimate_desc>This is comparing the Switching group to the Comparator group</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group.</title>
        <description>The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.</description>
        <time_frame>Pre-study (Enrollment), Day 1, Day 15, Week 24</time_frame>
        <population>Participants in the comparator group were assessed to have had two pre-study infusions at time of enrollment. A retrospective chart review was conducted to determine the number of IRRs experienced during these previous infusions. The collected number of IRRs was used as a comparison measure against the switching group.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.</description>
          </group>
          <group group_id="O2">
            <title>Comparator Group</title>
            <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group.</title>
          <description>The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.</description>
          <population>Participants in the comparator group were assessed to have had two pre-study infusions at time of enrollment. A retrospective chart review was conducted to determine the number of IRRs experienced during these previous infusions. The collected number of IRRs was used as a comparison measure against the switching group.</population>
          <units>Infusions</units>
          <param>Number</param>
          <units_analyzed>Infusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Infusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-study infusions</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Infusions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Infusions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Infusions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Infusions</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0000</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.0000</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.5299</ci_lower_limit>
            <ci_upper_limit>1.8872</ci_upper_limit>
            <estimate_desc>Comparing Switching group Day 1 to combined Comparator group</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0053</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>.2857</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.1006</ci_lower_limit>
            <ci_upper_limit>.8114</ci_upper_limit>
            <estimate_desc>Switching group Day 15 was compared to combined Comparator group.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6474</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>.8571</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.4385</ci_lower_limit>
            <ci_upper_limit>1.6753</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
        <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
        <time_frame>Day 1, pre-study infusions</time_frame>
        <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions prior to enrollment (as assessed via retrospective chart review). This analysis is comparing IRRs of the Switching group's Day 1 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Comparator Group</title>
            <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
          <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
          <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions prior to enrollment (as assessed via retrospective chart review). This analysis is comparing IRRs of the Switching group's Day 1 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
          <units>Infusions</units>
          <param>Number</param>
          <units_analyzed>Infusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Infusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86"/>
                    <measurement group_id="O2" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3, 4, or 5 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
        <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.</description>
        <time_frame>Day 15, pre-study infusions</time_frame>
        <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Day 15 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Comparator Group</title>
            <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
          <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.</description>
          <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Day 15 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
          <units>Infusions</units>
          <param>Number</param>
          <units_analyzed>Infusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Infusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96"/>
                    <measurement group_id="O2" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3, 4, and 5 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
        <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
        <time_frame>Week 24, pre-study infusions</time_frame>
        <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Week 24 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Comparator Group</title>
            <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions</title>
          <description>The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .</description>
          <population>The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Week 24 infusion, with the comparator group's pre-study infusion 1 and 2.</population>
          <units>Infusions</units>
          <param>Number</param>
          <units_analyzed>Infusions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Infusions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88"/>
                    <measurement group_id="O2" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3, 4, and 5 Infusion Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions</title>
        <description>We will also compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.</description>
        <time_frame>Day 1, Day 15, Week 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O3">
            <title>Switching Group - Week 24 Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions</title>
          <description>We will also compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0075</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>.2857</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.1072</ci_lower_limit>
            <ci_upper_limit>.7613</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5930</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>.8571</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.4868</ci_lower_limit>
            <ci_upper_limit>1.5093</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0209</p_value>
            <method>Generalized estimating equations</method>
            <method_desc>GEE was used because there are repeated measures on subjects.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>3.0000</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.1260</ci_lower_limit>
            <ci_upper_limit>7.9932</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of Ocrelizumab Anti-drug Anti-bodies</title>
        <description>Proportion of ocrelizumab patients who test positive for ocrelizumab anti-drug anti-bodies</description>
        <time_frame>Day 1 and Week 24</time_frame>
        <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Week 24 Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of Ocrelizumab Anti-drug Anti-bodies</title>
          <description>Proportion of ocrelizumab patients who test positive for ocrelizumab anti-drug anti-bodies</description>
          <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.03" upper_limit="5.45"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.03" upper_limit="5.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of Rituximab Anti-drug Anti-bodies</title>
        <description>Proportion of patients who test positive for rituximab anti-drug anti-bodies.</description>
        <time_frame>Day 1 and Week 24</time_frame>
        <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Week 24</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of Rituximab Anti-drug Anti-bodies</title>
          <description>Proportion of patients who test positive for rituximab anti-drug anti-bodies.</description>
          <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.00" lower_limit="8.81" upper_limit="23.19"/>
                    <measurement group_id="O2" value="7.00" lower_limit="2.86" upper_limit="13.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>B Cell Depletion (CD19)</title>
        <description>Proportion of patients with CD19% &lt;= 1%.</description>
        <time_frame>Day 1, Week 24, 1 Year</time_frame>
        <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Week 24</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O3">
            <title>Switching Group - 1 Year</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
        </group_list>
        <measure>
          <title>B Cell Depletion (CD19)</title>
          <description>Proportion of patients with CD19% &lt;= 1%.</description>
          <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.14" lower_limit="47.35" upper_limit="66.94"/>
                    <measurement group_id="O2" value="92.00" lower_limit="84.84" upper_limit="96.48"/>
                    <measurement group_id="O3" value="90.32" lower_limit="82.42" upper_limit="95.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>B Cell Depletion (CD20)</title>
        <description>Proportion of patients with CD20% &lt;= 1%</description>
        <time_frame>Day 1, Week 24, 1 Year</time_frame>
        <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Week 24</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
          <group group_id="O3">
            <title>Switching Group - 1 Year</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
          </group>
        </group_list>
        <measure>
          <title>B Cell Depletion (CD20)</title>
          <description>Proportion of patients with CD20% &lt;= 1%</description>
          <population>Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="88"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.70" lower_limit="46.84" upper_limit="66.56"/>
                    <measurement group_id="O2" value="92.00" lower_limit="84.84" upper_limit="96.48"/>
                    <measurement group_id="O3" value="88.64" lower_limit="82.01" upper_limit="95.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: Eotaxin - Pre-Post Infusion - Day 1</title>
        <description>Comparing Eotaxin concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: Eotaxin - Pre-Post Infusion - Day 1</title>
          <description>Comparing Eotaxin concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="117.44" spread="50.19"/>
                    <measurement group_id="O2" value="101.41" spread="55.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.005</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>--16.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-27.05</ci_lower_limit>
            <ci_upper_limit>-5.01</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IFN-gamma - Pre-Post Infusion - Day 1</title>
        <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IFN-gamma - Pre-Post Infusion - Day 1</title>
          <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.03" spread="1.42"/>
                    <measurement group_id="O2" value="4.58" spread="5.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.54</ci_lower_limit>
            <ci_upper_limit>3.56</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-10 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-10 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" spread="0.27"/>
                    <measurement group_id="O2" value="8.75" spread="11.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Median Difference (Net)</param_type>
            <param_value>8.58</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.33</ci_lower_limit>
            <ci_upper_limit>10.82</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.79" spread="38.79"/>
                    <measurement group_id="O2" value="52.42" spread="35.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-7.37</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.19</ci_lower_limit>
            <ci_upper_limit>-4.55</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-16 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-16 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.48" spread="40.77"/>
                    <measurement group_id="O2" value="129.80" spread="80.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>44.32</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>29.59</ci_lower_limit>
            <ci_upper_limit>59.05</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-1RA - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-1RA concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-1RA - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-1RA concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="196.71" spread="202.10"/>
                    <measurement group_id="O2" value="550.06" spread="920.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>353.35</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>175.23</ci_lower_limit>
            <ci_upper_limit>531.46</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-27 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-27 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-27 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-27 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="643.32" spread="269.50"/>
                    <measurement group_id="O2" value="820.23" spread="340.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>176.90</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>124.50</ci_lower_limit>
            <ci_upper_limit>229.31</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-6 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-6 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-6 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-6 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" spread="0.29"/>
                    <measurement group_id="O2" value="0.49" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0020</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.07</ci_lower_limit>
            <ci_upper_limit>0.32</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-7 - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-7 - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.84" spread="0.36"/>
                    <measurement group_id="O2" value="1.38" spread="2.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.32</ci_lower_limit>
            <ci_upper_limit>0.77</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-8(HA) - Pre-Post Infusion - Day 1</title>
        <description>Comparing IL-8(HA) concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-8(HA) - Pre-Post Infusion - Day 1</title>
          <description>Comparing IL-8(HA) concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="306.89" spread="186.64"/>
                    <measurement group_id="O2" value="260.73" spread="147.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0091</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-46.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-80.61</ci_lower_limit>
            <ci_upper_limit>-11.72</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MCP-1 - Pre-Post Infusion - Day 1</title>
        <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MCP-1 - Pre-Post Infusion - Day 1</title>
          <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.83" spread="14.37"/>
                    <measurement group_id="O2" value="90.09" spread="146.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>55.26</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>27.00</ci_lower_limit>
            <ci_upper_limit>83.52</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MDC - Pre-Post Infusion - Day 1</title>
        <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MDC - Pre-Post Infusion - Day 1</title>
          <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="468.96" spread="138.66"/>
                    <measurement group_id="O2" value="451.72" spread="139.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0044</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-17.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-28.96</ci_lower_limit>
            <ci_upper_limit>-5.51</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MIP-1alpha - Pre-Post Infusion - Day 1</title>
        <description>Comparing MIP-1alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MIP-1alpha - Pre-Post Infusion - Day 1</title>
          <description>Comparing MIP-1alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.50" spread="26.72"/>
                    <measurement group_id="O2" value="45.52" spread="34.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>16.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>9.75</ci_lower_limit>
            <ci_upper_limit>22.28</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MIP-1beta - Pre-Post Infusion - Day 1</title>
        <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MIP-1beta - Pre-Post Infusion - Day 1</title>
          <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.27" spread="9.63"/>
                    <measurement group_id="O2" value="453.35" spread="671.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>429.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>296.07</ci_lower_limit>
            <ci_upper_limit>562.10</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 1</title>
        <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 1</title>
          <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.90" spread="2.64"/>
                    <measurement group_id="O2" value="5.13" spread="5.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0101</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.30</ci_lower_limit>
            <ci_upper_limit>2.16</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: TARC - Pre-Post Infusion - Day 1</title>
        <description>Comparing TARC concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: TARC - Pre-Post Infusion - Day 1</title>
          <description>Comparing TARC concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.02" spread="13.54"/>
                    <measurement group_id="O2" value="32.72" spread="21.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>8.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.87</ci_lower_limit>
            <ci_upper_limit>12.52</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: TNF-alpha - Pre-Post Infusion - Day 1</title>
        <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
        <time_frame>Day 1</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 1 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 1 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: TNF-alpha - Pre-Post Infusion - Day 1</title>
          <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 1</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" spread="0.39"/>
                    <measurement group_id="O2" value="2.53" spread="2.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 1 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 99.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.04</ci_lower_limit>
            <ci_upper_limit>2.03</ci_upper_limit>
            <estimate_desc>Mean of post minus pre.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: Exotaxin - Pre-Post Infusion - Day 15</title>
        <description>Comparing Exotaxin concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: Exotaxin - Pre-Post Infusion - Day 15</title>
          <description>Comparing Exotaxin concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="128.38" spread="54.32"/>
                    <measurement group_id="O2" value="95.79" spread="60.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-33.17</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-38.91</ci_lower_limit>
            <ci_upper_limit>-27.44</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IFN-gamma - Pre-Post Infusion - Day 15</title>
        <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IFN-gamma - Pre-Post Infusion - Day 15</title>
          <description>Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.02" spread="1.37"/>
                    <measurement group_id="O2" value="1.40" spread="1.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0008</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.62</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.98</ci_lower_limit>
            <ci_upper_limit>-0.26</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-10 - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-10 - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" spread="0.12"/>
                    <measurement group_id="O2" value="2.12" spread="3.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.23</ci_lower_limit>
            <ci_upper_limit>2.79</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.36" spread="31.75"/>
                    <measurement group_id="O2" value="41.31" spread="29.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-7.84</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.87</ci_lower_limit>
            <ci_upper_limit>-5.81</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-16 - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-16 - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.35" spread="54.78"/>
                    <measurement group_id="O2" value="76.62" spread="29.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0022</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-14.20</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-23.15</ci_lower_limit>
            <ci_upper_limit>-5.25</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-1beta - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-1beta - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.65" spread="0.73"/>
                    <measurement group_id="O2" value="0.95" spread="0.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.17</ci_lower_limit>
            <ci_upper_limit>0.43</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-7 - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-7 - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88" spread="0.64"/>
                    <measurement group_id="O2" value="1.29" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.41</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.22</ci_lower_limit>
            <ci_upper_limit>0.61</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: IL-8 - Pre-Post Infusion - Day 15</title>
        <description>Comparing IL-8 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: IL-8 - Pre-Post Infusion - Day 15</title>
          <description>Comparing IL-8 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.82" spread="1.48"/>
                    <measurement group_id="O2" value="1.09" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.72</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.95</ci_lower_limit>
            <ci_upper_limit>-0.50</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MCP-1 - Pre-Post Infusion - Day 15</title>
        <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MCP-1 - Pre-Post Infusion - Day 15</title>
          <description>Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.57" spread="18.08"/>
                    <measurement group_id="O2" value="16.33" spread="9.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-19.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-22.64</ci_lower_limit>
            <ci_upper_limit>-15.98</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MCP-4 - Pre-Post Infusion - Day 15</title>
        <description>Comparing MCP-4 concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MCP-4 - Pre-Post Infusion - Day 15</title>
          <description>Comparing MCP-4 concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.38" spread="23.70"/>
                    <measurement group_id="O2" value="30.38" spread="15.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-6.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.85</ci_lower_limit>
            <ci_upper_limit>-4.08</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MDC - Pre-Post Infusion - Day 15</title>
        <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MDC - Pre-Post Infusion - Day 15</title>
          <description>Comparing MDC concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="458.13" spread="154.72"/>
                    <measurement group_id="O2" value="435.00" spread="165.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0061</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-23.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-39.66</ci_lower_limit>
            <ci_upper_limit>-6.78</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MIP-1beta - Pre-Post Infusion - Day 15</title>
        <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MIP-1beta - Pre-Post Infusion - Day 15</title>
          <description>Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.09" spread="9.46"/>
                    <measurement group_id="O2" value="17.23" spread="7.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.24</ci_lower_limit>
            <ci_upper_limit>-4.14</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 15</title>
        <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: MIP-3alpha - Pre-Post Infusion - Day 15</title>
          <description>Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.15" spread="4.32"/>
                    <measurement group_id="O2" value="3.31" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0077</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.84</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.45</ci_lower_limit>
            <ci_upper_limit>-0.23</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine: TNF-alpha - Pre-Post Infusion - Day 15</title>
        <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
        <time_frame>Day 15</time_frame>
        <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Switching Group - Day 15 - Pre Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Pre-Infusion</description>
          </group>
          <group group_id="O2">
            <title>Switching Group - Day 15 - Post Infusion</title>
            <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells&#xD;
Post-Infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine: TNF-alpha - Pre-Post Infusion - Day 15</title>
          <description>Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 15</description>
          <population>Change in mean concentration between pre and post infusion. Only cytokines with statistically significant pre-post changes reported.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.14" spread="0.45"/>
                    <measurement group_id="O2" value="0.81" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired T-test for change in means. Null hypothesis: no pre-post difference.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>99 patients with non-missing change scores used. Controlled for the false discovery rate (alpha = 0.05) for all cytokines on day 15 using the Benjamini-Hochberg procedure.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>Paired T-test. Degrees of freedom = 98.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.32</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.37</ci_lower_limit>
            <ci_upper_limit>-0.27</ci_upper_limit>
            <estimate_desc>Mean of post minus pre. 99 usable change scores.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year - enrollment to month 12 infusion.</time_frame>
      <desc>Because data for the comparator group was collected retrospectively using chart review, 0 participants in that group were at risk for All-Cause Mortality, and All-Cause Mortality was not monitored for that group.</desc>
      <group_list>
        <group group_id="E1">
          <title>Switching Group</title>
          <description>600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.&#xD;
Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells</description>
        </group>
        <group group_id="E2">
          <title>Comparator Group</title>
          <description>Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line&#xD;
Rituximab: A chimeric monoclonal antibody against CD20.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperammonemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hip Dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver and renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Unknown pulmonary complications</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="52" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="17" subjects_affected="14" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="47" subjects_affected="36" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="100"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Timothy Vollmer</name_or_title>
      <organization>University of Colorado Anschutz, Neurology Department</organization>
      <phone>3037242187</phone>
      <email>timothy.vollmer@ucdenver.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02980042
org study id: 16-1354
nct id: NCT02980042
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective between and within group observational study to determine differences
      in tolerability, immunogenicity and safety related outcomes for 100 multiple sclerosis (MS)
      patients who have been administered at least two infusions of rituximab, six months apart and
      are willing to be switched to ocrelizumab compared to a 100 patients who are continuing on
      rituximab as a comparison cohort from the clinic population treated as part of clinical care.
Studies of rituximab, a chimeric monoclonal antibody against CD20 have shown that B-cell
      depletion is of clinical beneﬁt as a potential treatment in relapsing forms of multiple
      sclerosis (MS).1 Ocrelizumab is a humanized monoclonal antibody that targets CD20 and
      selectively depletes CD20 expressing cells, while preserving the capacity for B cell
      reconstitution. When compared with rituximab, ocrelizumab is associated with increased
      antibody-dependent cell-mediated cytotoxic eﬀects, and reduced complement-dependent cytotoxic
      eﬀects in vitro.2 By increasing antibody-dependent cell mediated cytotoxic eﬀects,
      ocrelizumab might modulate tissue-dependent mechanisms of pathogenic response more eﬀectively
      compared to rituximab. As a humanized molecule, ocrelizumab is expected to be less
      immunogenic with repeated infusions and might thus present a more favorable safety profile
      when compared to rituximab.2

      Despite rituximab's current off label use in the treatment of MS, currently there is only
      data available from phase 2 trials. The HERMES group conducted a phase 2, double-blind,
      48-week trial involving 104 patients with relapsing forms of MS; 69 patients received 1000 mg
      of intravenous rituximab and 35 patients received placebo on days 1 and 15.3 A significantly
      higher number of patients in the rituximab group (78.3%) versus the placebo group (40.0%) had
      an infusion related reaction (IRR) events within 24 hours after the first infusion. Within 24
      hours after the second infusion, fewer patients in the rituximab group (20.3%) than in the
      placebo group (40%) had similar events. A majority of the rituximab group with IRR events
      (92.6%) were classified as mild to moderate (grade 1 or 2) in severity.

      Safety data from the Investigators Brochure on the OPERA I and II phase 3 trials comparing
      ocrelizumab to interferon β-1a on relapsing MS patients showed that IRRs were the most common
      adverse events experienced by patients treated with 600 mg of ocrelizumab.4 The percentage of
      patients experiencing IRRs was higher in the ocrelizumab group (relapsing forms of MS: 34.3%;
      primary progressive forms of MS 39.9%) compared with the interferon β-1a (active control)
      group who received placebo infusions (relapsing forms of MS: 9.7%; primary progressive forms
      of MS: 25.5%). The rate of IRRs was highest during the first infusion or Dose 1 (27.5% on Day
      1; 4.71% on Day 15 of Dose 1) and decreased over time (13.7%; 9.6% and 7.8% following Dose 2,
      3, and 4 respectively) for the ocrelizumab treated group. Comparatively, interferon β-1a
      users experienced 6.5% of IRRs on Day 1, 2.58% on Day 15, < 2.00% after doses 2, 3 and 4
      respectively. The reported IRRs were primarily mild-to-moderate in severity (Grades 1 and 2).
      Serious IRRs occurred in 0.1% and 1.0% respectively of relapsing and progressive patients and
      treated with ocrelizumab.

      Clinical data describing the efficacy and tolerability profile of rituximab and ocrelizumab
      has utilized populations with different prior treatment characteristics. In the phase 2
      HERMES trials, a majority (78.5%) of rituximab patients had been previously been treated with
      a disease modifying therapy in the last 2 years.3 In contrast, the OPERA I and II phase 3
      clinical trials, a majority of ocrelizumab patients (72.9% in OPERA I and 73.8% in OPERA II)
      represented a treatment naïve population.4 Examining IRRs in patients who have switched from
      rituximab to ocrelizumab versus those continuing on rituximab will examine the magnitude of
      the IRRs and subsequent tolerability of ocrelizumab in a real world population.

      Earlier concepts of MS disease pathology have suggested that pathogenic T cells are
      sufficient for the full expression of MS. However, it is now evident that full autoimmune B
      cells and humoral immune mechanisms also play key roles. 5 Ocrelizumab is a humanized
      monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells. CD20
      is a B cell surface molecule that is expressed on pre B cells and mature B cells, but not
      expressed earlier in the development of B cells or on mature plasma cells. In all three
      ocrelizumab studies (with relapsing and progressive populations), treatment with 600 mg of
      ocrelizumab led to rapid and complete depletion of circulating CD19+ B cells within 14 days
      post treatment. 4 B cell depletion was sustained throughout treatment period. The median time
      to repletion of B cells was 72 weeks (range 27-175 weeks). We hypothesize that in switching
      rituximab treated patients to ocrelizumab, the proportion of patients with B cell depletion
      (< 1%) 6 months after the first and third infusion of ocrelizumab will be the same as the
      baseline assessment which will be 6 months after the last dose of rituximab and similar to
      findings in OPERA I and II.

      Immunogenicity results from the OPERA I and II trials examined the number of patients who had
      treatment induced anti-drug antibodies (ADA) to ocrelizumab. 4 Of the 807 patients who
      received ocrelizumab and had an ADA assay from a post baseline sample during the controlled
      treatment period, 3 patients (0.4%) showed treatment induced ADA to ocrelizumab. Of these, 1
      patient tested positive for neutralizing antibodies (NAB) to ocrelizumab. During the open
      label extension phase, the prevalence of ADA continued to remain low with post baseline
      incidence of 1.9% (2/103 with treatment induced ADA). Currently there is little evidence
      examining the prevalence of treatment induced ADAs to both rituximab and ocrelizumab in
      patients that switch from the former to the latter in comparison to continuing rituximab
      patients. Therefore, we will perform assays to detect ADAs to both rituximab and ocrelizumab
      in all patients switching from rituximab to ocrelizumab at Day 1, 6 months and 12 months on
      ocrelizumab.

      Finally, IRRs have been hypothesized to be a reaction by autoantibodies to the treatment drug
      or possibly from the release of cytokines from CD20 expressing cells as they are destroyed by
      ocrelizumab causing a "cytokine storm". Understanding this process may lead to mechanisms
      that may aid in ameliorating these infusion reactions. If they are associated with ADA, then
      it might be possible to predictively premedicate these patients only. Alternatively, if they
      are associated with cytokine release, it may be possible to eliminate premedication in
      patients who are already CD20+cell depleted in subsequent infusions. Therefore, we will assay
      the profile of certain cytokines in the serum 4 hours after start of ocrelizumab infusion.

      With ocrelizumab expected to enter the MS therapeutic market within the next year, we expect
      third party payers within and outside the US will require that the FDA or EMA approved
      versions of anti-CD20 monoclonal antibodies be used in the treatment of MS, namely
      ocrelizumab. Currently, we estimate several thousand MS patients in the US and Sweden are
      taking rituximab currently. Thus, it will be important to demonstrate that switching from a
      chimeric anti-CD20 to a fully humanized anti-CD20 does not lead to unexpected infusion
      reactions and does not increase the probability of development of anti-drug antibodies.

      The Rocky Mountain MS Center (RMMSC) at the University of Colorado Anschutz Medical Campus
      prescribed rituximab infusions for 533 MS patients in the last 12 months, of which 323
      patients received their infusion at the University of Colorado Hospital's Outpatient Infusion
      Center between September, 2015-March, 2016. The RMMSC is one of the few sites nationwide with
      large numbers of MS patients treated with rituximab. With the anticipated approval of
      ocrelizumab, current rituximab users are being counselled by their MS providers at RMMSC to
      consider switching to ocrelizumab post approval, particularly if US Payers adopt the FDA
      approved version as the preferred anti-CD20 agent for MS.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Infusions With >= 1 IRR Between the Switching and Comparator Groups
time frame: Day 1, Day 15, Week 24
description: The investigators will report the proportion of infusions with >= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.
measure: Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group.
time frame: Pre-study (Enrollment), Day 1, Day 15, Week 24
description: The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.
measure: Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions
time frame: Day 1, pre-study infusions
description: The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .
measure: Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions
time frame: Day 15, pre-study infusions
description: The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.
measure: Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions
time frame: Week 24, pre-study infusions
description: The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .
measure: Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions
time frame: Day 1, Day 15, Week 24
description: We will also compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.
measure: Presence of Ocrelizumab Anti-drug Anti-bodies
time frame: Day 1 and Week 24
description: Proportion of ocrelizumab patients who test positive for ocrelizumab anti-drug anti-bodies
measure: Presence of Rituximab Anti-drug Anti-bodies
time frame: Day 1 and Week 24
description: Proportion of patients who test positive for rituximab anti-drug anti-bodies.
measure: B Cell Depletion (CD19)
time frame: Day 1, Week 24, 1 Year
description: Proportion of patients with CD19% <= 1%.
measure: B Cell Depletion (CD20)
time frame: Day 1, Week 24, 1 Year
description: Proportion of patients with CD20% <= 1%
measure: Cytokine: Eotaxin - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing Eotaxin concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IFN-gamma - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-10 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-16 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-1RA - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-1RA concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-27 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-27 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-6 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-6 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-7 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: IL-8(HA) - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing IL-8(HA) concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: MCP-1 - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: MDC - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing MDC concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: MIP-1alpha - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing MIP-1alpha concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: MIP-1beta - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: MIP-3alpha - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: TARC - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing TARC concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: TNF-alpha - Pre-Post Infusion - Day 1
time frame: Day 1
description: Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 1
measure: Cytokine: Exotaxin - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing Exotaxin concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IFN-gamma - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IFN-gamma concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-10 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-10 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-12/IL-23p40 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-12/IL-23p40 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-16 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-16 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-1beta - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-1beta concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-7 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-7 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: IL-8 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing IL-8 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: MCP-1 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing MCP-1 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: MCP-4 - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing MCP-4 concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: MDC - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing MDC concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: MIP-1beta - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing MIP-1beta concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: MIP-3alpha - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing MIP-3alpha concentration between pre and post ocrelizumab infusion - Day 15
measure: Cytokine: TNF-alpha - Pre-Post Infusion - Day 15
time frame: Day 15
description: Comparing TNF-alpha concentration between pre and post ocrelizumab infusion - Day 15
arm group label: Switching Group
arm group type: Experimental
description: 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.
arm group label: Comparator Group
arm group type: Active Comparator
description: Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line
intervention type: Drug
intervention name: Ocrelizumab
description: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
arm group label: Switching Group
other name: Ocrevus
intervention type: Drug
intervention name: Rituximab
description: A chimeric monoclonal antibody against CD20.
arm group label: Comparator Group
other name: Rituxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Timothy Vollmer, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Kavita Nair, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Enrique Alvarez, MD, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Rituximab
mesh term: Ocrelizumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 