<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/NCT01721161</url>
  </required_header>
  <id_info>
    <org_study_id>215ON201</org_study_id>
    <nct_id>NCT01721161</nct_id>
  </id_info>
  <brief_title>BIIB033 In Acute Optic Neuritis (AON)</brief_title>
  <official_title>A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With First Episode of Acute Optic Neuritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biogen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to evaluate the efficacy of BIIB033 in subjects with&#xD;
      their first episode of unilateral acute optic neuritis (AON). The secondary objective of this&#xD;
      study is to assess the safety, tolerability, and pharmacokinetics (PK) of BIIB033 in this&#xD;
      study population.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in FF-VEP Latency at Week 24: Per-protocol Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in LCLA at Week 24: Per-protocol Population</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>32 weeks</time_frame>
    <description>An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of BIIB033 Concentration</measure>
    <time_frame>Up to 32 weeks</time_frame>
    <description>One pre-dose pharmacokinetic (PK) sample and 1 post-dose PK sample (approximately between 1 and 3 hours after the end of IV infusion) were collected for all participants on Day 1 and at Weeks 4 through 20 (every 4 weeks). Additionally, only 1 PK sample was collected at Week 24 and Week 32. (There was no dosing on Week 24 and Week 32, so only one blood sample for BIIB033 concentration was taken.) Samples collected at early termination visits were treated as predose samples for the next scheduled visit.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Acute Optic Neuritis</condition>
  <arm_group>
    <arm_group_label>BIIB033</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BIIB033 (anti-LINGO-1 mAb)</intervention_name>
    <description>100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).</description>
    <arm_group_label>BIIB033</arm_group_label>
    <other_name>anti-LINGO-1 monoclonal antibody (mAb)</other_name>
    <other_name>Opicinumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide written consent and any authorization required by law.&#xD;
&#xD;
          -  Confirmed diagnosis of AON&#xD;
&#xD;
          -  All male or female subjects of childbearing potential must practice effective&#xD;
             contraception during the study and be willing and able to continue contraception for&#xD;
             at least 6 months after their last dose of study treatment.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Prior episode(s) of optic neuritis or loss of vision not due to AON.&#xD;
&#xD;
          -  Subjects with an established diagnosis of multiple sclerosis are excluded except if&#xD;
             newly diagnosed based on the current episode of AON and positive brain magnetic&#xD;
             resonance imaging results consistent with the 2010 revisions to the McDonald's&#xD;
             criteria.&#xD;
&#xD;
          -  Previous history of a clinically significant disease.&#xD;
&#xD;
          -  Females who have a positive pregnancy test result, or who are pregnant, breastfeeding,&#xD;
             or planning to conceive during the study.&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV), hepatitis C virus antibody, or&#xD;
             hepatitis B virus.&#xD;
&#xD;
          -  History or evidence of drug or alcohol abuse within 2 years prior to Screening.&#xD;
&#xD;
          -  Current enrollment in any other study treatment or disease study within 3 months prior&#xD;
             to Day 1/Baseline.&#xD;
&#xD;
        NOTE: Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parkville</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sidney</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brugge</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ghent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Limburg</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Halifax</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ottawa</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Olomouc</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Prague</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Glostrup</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bamberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dusseldorf</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tubingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fidenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cordoba</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Palmar</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Czech Republic</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Hong Kong</country>
  </removed_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>May 24, 2016</results_first_submitted>
  <results_first_submitted_qc>May 24, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 30, 2016</results_first_posted>
  <disposition_first_submitted>August 21, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>August 21, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">September 7, 2015</disposition_first_posted>
  <last_update_submitted>May 24, 2016</last_update_submitted>
  <last_update_submitted_qc>May 24, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 30, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Optic Neuritis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuritis</mesh_term>
    <mesh_term>Optic Neuritis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
        </group>
        <group group_id="P2">
          <title>BIIB033</title>
          <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
        </group>
        <group group_id="B2">
          <title>BIIB033</title>
          <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</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="41"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="82"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.4" spread="8.85"/>
                    <measurement group_id="B2" value="31.8" spread="7.17"/>
                    <measurement group_id="B3" value="32.1" spread="8.01"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Days from first AON symptom to first dose</title>
          <description>First dose given, on average, 2 weeks after completion of high-dose (1 g daily for 3 to 5 days) IV methylprednisolone treatment.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.6" spread="3.4"/>
                    <measurement group_id="B2" value="23.6" spread="4.0"/>
                    <measurement group_id="B3" value="24.1" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Days from confirmed AON diagnosis to first dose</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.2" spread="4.9"/>
                    <measurement group_id="B2" value="18.7" spread="4.7"/>
                    <measurement group_id="B3" value="19.0" spread="4.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Affected eye</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Right eye</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Left eye</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Criteria for AON diagnosis</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Decreased visual acuity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased color vision</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relative afferent pupillary defect</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual field defect</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ocular pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not specified</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>AON signs and symptoms at screening or baseline</title>
          <description>Symptoms were not uniformly tested in accordance with a predefined protocol.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Visual field defect</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Color desaturation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Uhthoff's symptom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swollen optic disc</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relative afferent pupillary defect</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>FF-VEP conduction block in the affected eye at baseline</title>
          <description>FF-VEP=full-field visual evoked potentials</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>FF-VEP conduction block</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No FF-VEP conduction block</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>FF-VEP latency in the fellow eye at baseline</title>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="101.7" spread="5.25"/>
                    <measurement group_id="B2" value="102.7" spread="6.4"/>
                    <measurement group_id="B3" value="102.2" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>RGCL/IPL thickness in the affected eye at baseline</title>
          <description>RGCL/IPL=retinal ganglion cell layer/inner plexiform retinal layer. n=38 in the placebo group and n=40 in the anti-LINGO-1 group, total n=78.</description>
          <units>microns</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.0" spread="6.9"/>
                    <measurement group_id="B2" value="63.8" spread="7.4"/>
                    <measurement group_id="B3" value="64.8" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Brain Gd+ lesions before first dose</title>
          <description>Gd+=gadolinium-enhancing. n=38 in each group, total n=76.</description>
          <units>lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.5" spread="1.6"/>
                    <measurement group_id="B2" value="0.2" spread="1.0"/>
                    <measurement group_id="B3" value="0.4" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Volume of brain T2 lesions before first dose</title>
          <description>n=38 in each group, total n=76.</description>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.09" spread="1.32"/>
                    <measurement group_id="B2" value="1.09" spread="1.90"/>
                    <measurement group_id="B3" value="1.09" spread="1.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population</title>
        <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo). Last observation carried forward (LOCF) imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population</title>
          <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
          <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo). Last observation carried forward (LOCF) imputation was used if Week 24 data were missing.</population>
          <units>msec</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.83" spread="2.53"/>
                    <measurement group_id="O2" value="17.34" spread="2.53"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3337</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-3.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.61</ci_lower_limit>
            <ci_upper_limit>3.65</ci_upper_limit>
            <estimate_desc>Difference is calculated as BIIB033 100 mg/kg - placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population</title>
        <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) and a valid RNFL assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population</title>
          <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
          <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) and a valid RNFL assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.77" spread="2.08"/>
                    <measurement group_id="O2" value="-15.66" spread="2.03"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.1868</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-3.89</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.70</ci_lower_limit>
            <ci_upper_limit>1.92</ci_upper_limit>
            <estimate_desc>Difference is calculated as BIIB033 100 mg/kg - placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population</title>
        <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population</title>
          <description>Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.</description>
          <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.22" spread="2.26"/>
                    <measurement group_id="O2" value="-16.98" spread="2.33"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.1488</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-4.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.26</ci_lower_limit>
            <ci_upper_limit>1.74</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population</title>
        <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with a valid RGCL/IPL assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population</title>
          <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
          <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with a valid RGCL/IPL assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
          <units>µm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.90" spread="1.20"/>
                    <measurement group_id="O2" value="-11.05" spread="1.18"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4975</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-1.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.51</ci_lower_limit>
            <ci_upper_limit>2.21</ci_upper_limit>
            <estimate_desc>Difference is calculated as BIIB033 100 mg/kg - placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population</title>
        <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population</title>
          <description>Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.</description>
          <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
          <units>µm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.17" spread="1.29"/>
                    <measurement group_id="O2" value="-11.93" spread="1.35"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.3505</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-1.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.50</ci_lower_limit>
            <ci_upper_limit>1.98</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population</title>
        <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with an LCLA assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population</title>
          <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
          <population>ITT population: all randomized subjects who received at least 1 dose of study treatment (BIIB033 or placebo) with an LCLA assessment at Baseline. LOCF imputation was used if Week 24 data were missing.</population>
          <units>letters on a chart</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LCLA 1.25% chart</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="1.8"/>
                    <measurement group_id="O2" value="6.5" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LCLA 2.5% chart</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.9" spread="2.0"/>
                    <measurement group_id="O2" value="11.0" spread="2.0"/>
                  </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>LCLA 1.25% chart</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5371</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.9</ci_lower_limit>
            <ci_upper_limit>3.6</ci_upper_limit>
            <estimate_desc>Difference is calculated as BIIB033 100 mg/kg - placebo.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>LCLA 2.5% chart</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.7741</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.5</ci_lower_limit>
            <ci_upper_limit>4.9</ci_upper_limit>
            <estimate_desc>Difference is calculated as BIIB033 100 mg/kg - placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in LCLA at Week 24: Per-protocol Population</title>
        <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in LCLA at Week 24: Per-protocol Population</title>
          <description>Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.</description>
          <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive MS-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
          <units>letters on a chart</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LCLA 1.25% chart</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" spread="1.8"/>
                    <measurement group_id="O2" value="6.0" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LCLA 2.5% chart</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="2.0"/>
                    <measurement group_id="O2" value="10.8" spread="2.2"/>
                  </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>LCLA 1.25% chart</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6645</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.6</ci_lower_limit>
            <ci_upper_limit>4.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>LCLA 2.5%</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8015</p_value>
            <method>ANCOVA</method>
            <param_type>DIfference</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.7</ci_lower_limit>
            <ci_upper_limit>5.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in FF-VEP Latency at Week 24: Per-protocol Population</title>
        <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS)-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in FF-VEP Latency at Week 24: Per-protocol Population</title>
          <description>Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.</description>
          <population>Per-protocol Population: participants from the ITT population who completed the study, did not miss more than 1 dose of BIIB033 or placebo, and did not receive multiple sclerosis (MS)-modifying therapies during the study period, which were prohibited per protocol. LOCF imputation was used if Week 24 data were missing.</population>
          <units>msec</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.24" spread="2.61"/>
                    <measurement group_id="O2" value="14.69" spread="2.72"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0504</p_value>
            <method>ANCOVA</method>
            <param_type>Difference</param_type>
            <param_value>-7.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-15.12</ci_lower_limit>
            <ci_upper_limit>0.01</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.</description>
        <time_frame>32 weeks</time_frame>
        <population>Safety population: all participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
          <group group_id="O2">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.</description>
          <population>Safety population: all participants who received at least 1 dose of study treatment.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with an event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with a moderate or severe event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with a severe event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with a related event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with a serious event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with a related serious event</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>Participants discontinuing treatment due to event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants withdrawing from study due to event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of BIIB033 Concentration</title>
        <description>One pre-dose pharmacokinetic (PK) sample and 1 post-dose PK sample (approximately between 1 and 3 hours after the end of IV infusion) were collected for all participants on Day 1 and at Weeks 4 through 20 (every 4 weeks). Additionally, only 1 PK sample was collected at Week 24 and Week 32. (There was no dosing on Week 24 and Week 32, so only one blood sample for BIIB033 concentration was taken.) Samples collected at early termination visits were treated as predose samples for the next scheduled visit.</description>
        <time_frame>Up to 32 weeks</time_frame>
        <population>PK analysis population: all participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data on record. n=number of participants with a sample at given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BIIB033</title>
            <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of BIIB033 Concentration</title>
          <description>One pre-dose pharmacokinetic (PK) sample and 1 post-dose PK sample (approximately between 1 and 3 hours after the end of IV infusion) were collected for all participants on Day 1 and at Weeks 4 through 20 (every 4 weeks). Additionally, only 1 PK sample was collected at Week 24 and Week 32. (There was no dosing on Week 24 and Week 32, so only one blood sample for BIIB033 concentration was taken.) Samples collected at early termination visits were treated as predose samples for the next scheduled visit.</description>
          <population>PK analysis population: all participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data on record. n=number of participants with a sample at given timepoint.</population>
          <units>µg/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline predose; n=41</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline postdose; n=40</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2030.00" lower_limit="1370.00" upper_limit="3200.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 predose; n=41</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="375.00" lower_limit="14.60" upper_limit="2960.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 postdose; n=37</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2350.00" lower_limit="368.00" upper_limit="3590.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 predose; n=38</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="537.00" lower_limit="32.70" upper_limit="1130.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 postdose; n=36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2585.00" lower_limit="550.00" upper_limit="4220.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 predose; n=36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="622.00" lower_limit="39.90" upper_limit="3230.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 postdose; n=34</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2695.00" lower_limit="542.00" upper_limit="4240.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16 predose; n=35</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="593.00" lower_limit="173.00" upper_limit="1320.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16 postdose; n=34</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2500.00" lower_limit="1560.00" upper_limit="4590.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20 predose; n=37</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="673.00" lower_limit="107.00" upper_limit="4760.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20 postdose; n=35</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2530.00" lower_limit="366.00" upper_limit="3990.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24; n=37</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="624.00" lower_limit="4.30" upper_limit="1060.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32; n=33</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.70" lower_limit="2.56" upper_limit="339.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were monitored from administration of first dose of study treatment through to Week 32 visit. SAEs were monitored from signing of the Informed Consent Form (ICF) through to Week 32 visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
        </group>
        <group group_id="E2">
          <title>BIIB033 100 mg/kg</title>
          <description>BIIB033 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral pericarditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple sclerosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Multiple sclerosis relapse</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Optic neuritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>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="25" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Colour blindness acquired</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Multiple sclerosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Uhthoff's phenomenon</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Visual field defect</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="41"/>
              </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>Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Biogen Study Medical Director</name_or_title>
      <organization>Biogen</organization>
      <email>clinicaltrials@biogen.com</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/NCT01721161
org study id: 215ON201
nct id: NCT01721161
lead sponsor: 
has dmc: Yes
The primary objective of the study is to evaluate the efficacy of BIIB033 in subjects with
      their first episode of unilateral acute optic neuritis (AON). The secondary objective of this
      study is to assess the safety, tolerability, and pharmacokinetics (PK) of BIIB033 in this
      study population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Full-field Visual Evoked Potential (FF-VEP) Latency at Week 24: Intent-to-treat (ITT) Population
time frame: Baseline, Week 24
description: Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.
measure: Change in FF-VEP Latency at Week 24: Per-protocol Population
time frame: Baseline, Week 24
description: Adjusted mean change in optic nerve conduction velocity (NCV) at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. Adjusted for the baseline latency of fellow eye.
measure: Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 24: ITT Population
time frame: Baseline, Week 24
description: Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.
measure: Percentage Change in SD-OCT Average RNFL Thickness at Week 24: Per-protocol Population
time frame: Baseline, Week 24
description: Adjusted mean percentage change in thickness of the RNFL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by SD-OCT. Percentage change is calculated as (affected eye - baseline of fellow eye)/baseline of fellow eye*100. Adjusted for the baseline RNFL thickness.
measure: Change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 24: ITT Population
time frame: Baseline, Week 24
description: Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.
measure: Change in SD-OCT Average RGCL/IPL at Week 24: Per-protocol Population
time frame: Baseline, Week 24
description: Adjusted mean change in thicknesses of the RGCL/IPL at Week 24 for the affected eye from the baseline of unaffected fellow eye as determined by segmentation of SD-OCT. Adjusted for the baseline RGCL/IPL thickness.
measure: Change in Low-contrast Letter Acuity (LCLA) at Week 24: ITT Population
time frame: Baseline, Week 24
description: Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.
measure: Change in LCLA at Week 24: Per-protocol Population
time frame: Baseline, Week 24
description: Adjusted mean change in LCLA at Week 24 from baseline as determined by 1.25% and 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value. The fellow eye is the reference eye for the inter-eye asymmetry. The range for LCLA assessment is 0-60.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: 32 weeks
description: An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
measure: Summary of BIIB033 Concentration
time frame: Up to 32 weeks
description: One pre-dose pharmacokinetic (PK) sample and 1 post-dose PK sample (approximately between 1 and 3 hours after the end of IV infusion) were collected for all participants on Day 1 and at Weeks 4 through 20 (every 4 weeks). Additionally, only 1 PK sample was collected at Week 24 and Week 32. (There was no dosing on Week 24 and Week 32, so only one blood sample for BIIB033 concentration was taken.) Samples collected at early termination visits were treated as predose samples for the next scheduled visit.
arm group label: BIIB033
arm group type: Experimental
description: Participants will receive BIIB033 once every 4 weeks for 20 weeks (a total of 6 doses).
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive Placebo via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
intervention type: Biological
intervention name: BIIB033 (anti-LINGO-1 mAb)
description: 100 mg/kg via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses).
arm group label: BIIB033
other name: anti-LINGO-1 monoclonal antibody (mAb)
other name: Opicinumab
intervention type: Drug
intervention name: Placebo
description: via IV infusion once every 4 weeks for 20 weeks (a total of 6 doses)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
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country: Australia
country: Belgium
country: Canada
country: Czech Republic
country: Denmark
country: Germany
country: Hungary
country: Italy
country: Spain
country: Sweden
country: United Kingdom
country: Hong Kong
responsible party type: Sponsor
mesh term: Neuritis
mesh term: Optic Neuritis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 