<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/NCT03283371</url>
  </required_header>
  <id_info>
    <org_study_id>101EP201</org_study_id>
    <secondary_id>2017-001995-45</secondary_id>
    <nct_id>NCT03283371</nct_id>
  </id_info>
  <brief_title>Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy</brief_title>
  <acronym>OPUS</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Exploring the Efficacy, Safety, and Tolerability of Natalizumab (BG00002) as Adjunctive Therapy in Adult Subjects With Drug-Resistant Focal Epilepsy</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary efficacy objective of the study is to determine if adjunctive therapy of&#xD;
      natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult&#xD;
      participants with drug-resistant focal epilepsy. The secondary efficacy objective is to&#xD;
      assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on&#xD;
      additional measures of seizure frequency.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 20, 2018</start_date>
  <completion_date type="Actual">November 18, 2020</completion_date>
  <primary_completion_date type="Actual">January 11, 2020</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>
    <intervention_model_description>This is a 6-month randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of natalizumab as adjunctive therapy in the treatment of adult subjects with drug-resistant focal epilepsy. The placebo-controlled phase is followed by a 6-month open-label phase during which all subjects receive natalizumab.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment</measure>
    <time_frame>Baseline, Week 8 to Week 24</time_frame>
    <description>Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Responders During Weeks 8 to 24 of Treatment</measure>
    <time_frame>Week 8 to Week 24</time_frame>
    <description>Responders were defined as participants with &gt;=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment</measure>
    <time_frame>Week 8 to Week 24</time_frame>
    <description>Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment</measure>
    <time_frame>Baseline, Week 8, Week 12, Week 16, Week 20, Week 24</time_frame>
    <description>Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment</measure>
    <time_frame>Week 8 to Week 24</time_frame>
    <description>Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)</time_frame>
    <description>An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Clinically Significant Laboratory Abnormalities</measure>
    <time_frame>From first dose up to 16 weeks after the last dose of study treatment (up to Week 60)</time_frame>
    <description>The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score</measure>
    <time_frame>Placebo-controlled Phase: Baseline, Weeks 4, 8, 12, 16, 20 and 24; Open-label Phase: Baseline, Weeks 28, 32, 36, 40, 44, 48 and 60/End of Study (EOS)</time_frame>
    <description>C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 1=Wish to be Dead; 2=Nonspecific Active Suicidal Thoughts; 3=Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4=Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5=Active Suicidal Ideation with Specific Plan and Intent; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Epilepsy, Focal Seizures, Partial Seizures</condition>
  <arm_group>
    <arm_group_label>Natalizumab 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab 300 mg intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will continue to receive natalizumab 300 mg IV infusion every 4 weeks for up to an additional 24 weeks in open label phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab matching placebo intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will then receive natalizumab 300 mg IV infusion every 4 weeks for 24 weeks in open label phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Natalizumab</intervention_name>
    <description>As specified in the treatment arm.</description>
    <arm_group_label>Natalizumab 300 mg</arm_group_label>
    <other_name>Tysabri</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>As specified in treatment arms.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Must have focal epilepsy diagnosed on clinical grounds and as applicable supported by&#xD;
             electroencephalogram findings [Scheffer 2017] and brain imaging. Participants with&#xD;
             multifocal epilepsy may be included if all other entry criteria are met.&#xD;
&#xD;
          -  Must have a drug-resistant epilepsy defined as failure of adequate trials of 2 (or&#xD;
             more) tolerated and appropriately chosen and used AEDs (whether as monotherapies or in&#xD;
             combination) [Kwan 2010].&#xD;
&#xD;
          -  Experiences 6 or more seizures during the 6-week prospective baseline period and is&#xD;
             not seizure free for more than 21 consecutive days during the prospective baseline&#xD;
             period&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Focal aware seizures without motor signs are the only seizure type.&#xD;
&#xD;
          -  Diagnosis of generalized, combined generalized and focal, or unknown epilepsy&#xD;
&#xD;
          -  Known progressive structural CNS lesion.&#xD;
&#xD;
          -  History of seizures occurring in predominantly clustered patterns, as determined by&#xD;
             the Investigator, over the 12 months prior to the Screening Visit (Week -6) or during&#xD;
             the 6-week prospective baseline period, where individual seizures cannot be counted.&#xD;
&#xD;
          -  History of status epilepticus within the previous 6 months.&#xD;
&#xD;
          -  Known history or presence of non-epileptic seizures.&#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>75 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>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tallahassee</city>
        <state>Florida</state>
        <zip>32308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Camden</city>
        <state>New Jersey</state>
        <zip>08103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Renton</city>
        <state>Washington</state>
        <zip>98055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <results_first_submitted>December 24, 2020</results_first_submitted>
  <results_first_submitted_qc>April 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 27, 2021</results_first_posted>
  <last_update_submitted>November 17, 2021</last_update_submitted>
  <last_update_submitted_qc>November 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Resistant Focal Epilepsy, Natalizumab, Seizure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Epilepsies, Partial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Natalizumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT03283371/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT03283371/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 31 investigational sites in United States from 20 March 2018 to 18 Nov 2020.</recruitment_details>
      <pre_assignment_details>A total 67 participants with drug-resistant focal epilepsy were enrolled and randomized in this study. Of which, 66 participants received at least one dose of study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo (Placebo-controlled Phase)</title>
          <description>Participants received natalizumab-matching placebo intravenous (IV) infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
        </group>
        <group group_id="P2">
          <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
          <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
        </group>
        <group group_id="P3">
          <title>Placebo to Natalizumab 300 mg (Open-label Phase)</title>
          <description>Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
        </group>
        <group group_id="P4">
          <title>Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)</title>
          <description>Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Placebo-controlled</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="33"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number of Participants Dosed</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="30"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </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 group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participants Did Not Receive Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-label Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="31"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="27"/>
                <participants group_id="P4" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Intent to Treat (ITT) population is defined as all participants who were randomized and received any dose of study treatment. Ethnicity was not collected in this study.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo (Placebo-controlled Phase)</title>
          <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
        </group>
        <group group_id="B2">
          <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
          <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</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="34"/>
            <count group_id="B2" value="32"/>
            <count group_id="B3" value="66"/>
          </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="39.1" spread="12.17"/>
                    <measurement group_id="B2" value="42.8" spread="14.56"/>
                    <measurement group_id="B3" value="40.9" spread="13.41"/>
                  </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="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment</title>
        <description>Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.</description>
        <time_frame>Baseline, Week 8 to Week 24</time_frame>
        <population>ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment</title>
          <description>Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.</description>
          <population>ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
          <units>log(seizure/28 days)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.43" spread="0.162"/>
                    <measurement group_id="O2" value="-0.58" spread="0.165"/>
                  </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>Analysis is based on MMRM and adjusted for natural log-transformed baseline seizure frequency, high seizure frequency category (&gt;=24 seizures and &lt;24 seizures), structural etiology category (yes and no), visit, treatment and treatment by visit interaction. An unstructured variance-covariance matrix is used in the model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5053</p_value>
            <method>Mixed Model for Repeated Measures (MMRM)</method>
            <param_type>LS Mean logarithmic difference</param_type>
            <param_value>-0.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.62</ci_lower_limit>
            <ci_upper_limit>0.31</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Responders During Weeks 8 to 24 of Treatment</title>
        <description>Responders were defined as participants with &gt;=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
        <time_frame>Week 8 to Week 24</time_frame>
        <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders During Weeks 8 to 24 of Treatment</title>
          <description>Responders were defined as participants with &gt;=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
          <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
          <units>percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.6"/>
                    <measurement group_id="O2" value="31.3"/>
                  </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>Based on logistic regression with a term for treatment group and with adjustment for natural log-transformed baseline seizure frequency, high seizure frequency category (&gt;=24 seizures and &lt;24 seizures) and structural etiology category (yes and no).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2231</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.64</ci_lower_limit>
            <ci_upper_limit>6.85</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment</title>
        <description>Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.</description>
        <time_frame>Week 8 to Week 24</time_frame>
        <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, &quot;number of participants analyzed&quot; signifies number of participants who were analyzed in this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment</title>
          <description>Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.</description>
          <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, &quot;number of participants analyzed&quot; signifies number of participants who were analyzed in this outcome measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment</title>
        <description>Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
        <time_frame>Baseline, Week 8, Week 12, Week 16, Week 20, Week 24</time_frame>
        <population>ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, &quot;number analyzed&quot; signifies number of participants analyzed at specific timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment</title>
          <description>Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.</description>
          <population>ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, &quot;number analyzed&quot; signifies number of participants analyzed at specific timepoint.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.23" spread="7.347"/>
                    <measurement group_id="O2" value="17.54" spread="7.223"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.33" spread="50.740"/>
                    <measurement group_id="O2" value="39.23" spread="130.988"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.41" spread="52.613"/>
                    <measurement group_id="O2" value="32.59" spread="104.775"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.40" spread="43.380"/>
                    <measurement group_id="O2" value="44.04" spread="153.714"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.48" spread="101.318"/>
                    <measurement group_id="O2" value="40.44" spread="144.768"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.27" spread="47.125"/>
                    <measurement group_id="O2" value="33.92" spread="114.436"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment</title>
        <description>Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.</description>
        <time_frame>Week 8 to Week 24</time_frame>
        <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment</title>
          <description>Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.</description>
          <population>The ITT population is defined as all participants who were randomized and received any dose of study treatment.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                  </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>Based on the logistic regression model with a term for treatment group and with adjustment for log-transformed baseline seizure frequency, high seizure frequency category (&gt;=24 seizures and &lt;24 seizures) and structural etiology category (yes and no) are considered as covariates.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6854</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.67</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.10</ci_lower_limit>
            <ci_upper_limit>4.57</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.</description>
        <time_frame>From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)</time_frame>
        <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O3">
            <title>Placebo to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
          <group group_id="O4">
            <title>Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.</description>
          <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="31"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Clinically Significant Laboratory Abnormalities</title>
        <description>The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.</description>
        <time_frame>From first dose up to 16 weeks after the last dose of study treatment (up to Week 60)</time_frame>
        <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O3">
            <title>Placebo to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
          <group group_id="O4">
            <title>Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Laboratory Abnormalities</title>
          <description>The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.</description>
          <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="31"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score</title>
        <description>C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 1=Wish to be Dead; 2=Nonspecific Active Suicidal Thoughts; 3=Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4=Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5=Active Suicidal Ideation with Specific Plan and Intent; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.</description>
        <time_frame>Placebo-controlled Phase: Baseline, Weeks 4, 8, 12, 16, 20 and 24; Open-label Phase: Baseline, Weeks 28, 32, 36, 40, 44, 48 and 60/End of Study (EOS)</time_frame>
        <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O2">
            <title>Natalizumab 300 mg (Placebo-controlled Phase)</title>
            <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
          </group>
          <group group_id="O3">
            <title>Placebo to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
          <group group_id="O4">
            <title>Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)</title>
            <description>Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score</title>
          <description>C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 1=Wish to be Dead; 2=Nonspecific Active Suicidal Thoughts; 3=Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4=Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5=Active Suicidal Ideation with Specific Plan and Intent; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.</description>
          <population>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="31"/>
                <count group_id="O4" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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>Week 20: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                    <count group_id="O2" value="32"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 28: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 40: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 44: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48: Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 60/End of Study (EOS): Suicidal Ideation or Behavior (1-10)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="31"/>
                    <count group_id="O4" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)</time_frame>
      <desc>The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo (Placebo-controlled Phase)</title>
          <description>Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
        </group>
        <group group_id="E2">
          <title>Natalizumab 300 mg (Placebo- Controlled Phase)</title>
          <description>Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.</description>
        </group>
        <group group_id="E3">
          <title>Placebo to Natalizumab 300 mg (Open-label Phase)</title>
          <description>Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
        </group>
        <group group_id="E4">
          <title>Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)</title>
          <description>Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Seizure cluster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</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="15" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="30"/>
              </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>US Biogen Clinical Trial Center</name_or_title>
      <organization>Biogen</organization>
      <phone>866-633-4636</phone>
      <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/NCT03283371
org study id: 101EP201
secondary id: 2017-001995-45
nct id: NCT03283371
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary efficacy objective of the study is to determine if adjunctive therapy of
      natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult
      participants with drug-resistant focal epilepsy. The secondary efficacy objective is to
      assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on
      additional measures of seizure frequency.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a 6-month randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of natalizumab as adjunctive therapy in the treatment of adult subjects with drug-resistant focal epilepsy. The placebo-controlled phase is followed by a 6-month open-label phase during which all subjects receive natalizumab.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double-blind
measure: Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
time frame: Baseline, Week 8 to Week 24
description: Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.
measure: Percentage of Responders During Weeks 8 to 24 of Treatment
time frame: Week 8 to Week 24
description: Responders were defined as participants with >=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
measure: Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment
time frame: Week 8 to Week 24
description: Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.
measure: Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment
time frame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
description: Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
measure: Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment
time frame: Week 8 to Week 24
description: Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)
description: An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
time frame: From first dose up to 16 weeks after the last dose of study treatment (up to Week 60)
description: The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.
measure: Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score
time frame: Placebo-controlled Phase: Baseline, Weeks 4, 8, 12, 16, 20 and 24; Open-label Phase: Baseline, Weeks 28, 32, 36, 40, 44, 48 and 60/End of Study (EOS)
description: C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 1=Wish to be Dead; 2=Nonspecific Active Suicidal Thoughts; 3=Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4=Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5=Active Suicidal Ideation with Specific Plan and Intent; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.
arm group label: Natalizumab 300 mg
arm group type: Experimental
description: Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab 300 mg intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will continue to receive natalizumab 300 mg IV infusion every 4 weeks for up to an additional 24 weeks in open label phase.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab matching placebo intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will then receive natalizumab 300 mg IV infusion every 4 weeks for 24 weeks in open label phase.
intervention type: Drug
intervention name: Natalizumab
description: As specified in the treatment arm.
arm group label: Natalizumab 300 mg
other name: Tysabri
intervention type: Other
intervention name: Placebo
description: As specified in treatment arms.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
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country: United States
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Seizures
mesh term: Epilepsies, Partial
mesh term: Natalizumab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 