<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/NCT02211209</url>
  </required_header>
  <id_info>
    <org_study_id>ISIS 304801-CS6</org_study_id>
    <secondary_id>2014-002421-35</secondary_id>
    <nct_id>NCT02211209</nct_id>
  </id_info>
  <brief_title>The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ionis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Akcea Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ionis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</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 purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52&#xD;
      weeks in participants with Familial Chylomicronemia Syndrome&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">March 28, 2017</completion_date>
  <primary_completion_date type="Actual">December 19, 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)</measure>
    <time_frame>Baseline to an on-treatment assessment between Week 13 and Week 19</time_frame>
    <description>Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline in Fasting TG at Month 3</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Response Rate Defined as Participants With Fasting Plasma TG &lt; 750 mg/dL at Month 3</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period</measure>
    <time_frame>Baseline to 12 months</time_frame>
    <description>Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period</measure>
    <time_frame>12 months</time_frame>
    <description>Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Familial Chylomicronemia Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Volanesorsen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Volanesorsen</intervention_name>
    <arm_group_label>Volanesorsen</arm_group_label>
    <other_name>ISIS 304801</other_name>
    <other_name>ApoC-III</other_name>
    <other_name>Approach</other_name>
    <other_name>IONIS-APOCIIIRx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of chylomicronemia&#xD;
&#xD;
          -  A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia)&#xD;
&#xD;
          -  Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%&#xD;
&#xD;
          -  Other types of severe hypertriglyceridemia&#xD;
&#xD;
          -  Active pancreatitis within 4 weeks of screening&#xD;
&#xD;
          -  Acute Coronary Syndrome within 6 months of screening&#xD;
&#xD;
          -  Major surgery within 3 months of screening&#xD;
&#xD;
          -  Treatment with Glybera therapy within 2 years of screening&#xD;
&#xD;
          -  Previous treatment with IONIS-APOCIIIRx&#xD;
&#xD;
          -  Have any other conditions in the opinion of the investigator which could interfere&#xD;
             with the participant participating in or completing the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <zip>92024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Campinas</city>
        <zip>13059-740</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04039-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <zip>G7H 5H6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Sainte-Foy</city>
        <state>Quebec</state>
        <zip>G1V 4M6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Szikszo</city>
        <zip>3800</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Safed</city>
        <zip>13110</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Milan</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Palermo</city>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Rome</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3000</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Cape Town</city>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Zaragoza</city>
        <state>Aragon</state>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>La Coruna</city>
        <state>Galicia</state>
        <zip>15001</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9LT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IONIS Investigative Site</name>
      <address>
        <city>Peterborough</city>
        <zip>PE3 9GZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944.</citation>
    <PMID>31390500</PMID>
  </results_reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <results_first_submitted>January 13, 2022</results_first_submitted>
  <results_first_submitted_qc>March 17, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <disposition_first_submitted>May 7, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>May 7, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 9, 2018</disposition_first_posted>
  <last_update_submitted>March 17, 2022</last_update_submitted>
  <last_update_submitted_qc>March 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type I</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>67 participants were randomized at 40 study centers in the United States, Canada, Brazil, France, Germany, Israel, Italy, Netherlands, South Africa, Spain, and the United Kingdom.</recruitment_details>
      <pre_assignment_details>67 participants were randomized, and 66 received study drug. The study included an 8-week screening period (including a diet-stabilization period), a 52-week treatment period, and a 13-week post-treatment evaluation period.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Volanesorsen</title>
          <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Dosed</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Investigator judgment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Voluntary withdrawal</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event or Serious Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason Not Specified</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety set included all randomized participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Volanesorsen</title>
          <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</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="33"/>
            <count group_id="B2" value="33"/>
            <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="46" spread="14"/>
                    <measurement group_id="B2" value="47" spread="13"/>
                    <measurement group_id="B3" value="46" spread="13"/>
                  </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="19"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other Race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Africa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fasting Triglycerides</title>
          <units>milligrams per deciliter (mg/dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2152" spread="1153"/>
                    <measurement group_id="B2" value="2267" spread="1259"/>
                    <measurement group_id="B3" value="2209" spread="1199"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3</title>
        <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
        <time_frame>Baseline to 3 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3</title>
          <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.6" lower_limit="-4.0" upper_limit="39.2"/>
                    <measurement group_id="O2" value="-76.5" lower_limit="-97.4" upper_limit="-55.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-94.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-121.7</ci_lower_limit>
            <ci_upper_limit>-66.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)</title>
        <description>Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.</description>
        <time_frame>Baseline to an on-treatment assessment between Week 13 and Week 19</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Data were reported for evaluable participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)</title>
          <description>Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Data were reported for evaluable participants.</population>
          <units>millimole hours per liter (mmol*h/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.92" spread="121.54"/>
                    <measurement group_id="O2" value="-234.77" spread="94.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline in Fasting TG at Month 3</title>
        <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
        <time_frame>Baseline to 3 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Fasting TG at Month 3</title>
          <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>mg/dL</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92" lower_limit="-301" upper_limit="486"/>
                    <measurement group_id="O2" value="-1712" lower_limit="-2094" upper_limit="-1330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1804</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>251</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2306</ci_lower_limit>
            <ci_upper_limit>-1302</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Response Rate Defined as Participants With Fasting Plasma TG &lt; 750 mg/dL at Month 3</title>
        <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter</description>
        <time_frame>Baseline to 3 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Data were reported for evaluable participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Response Rate Defined as Participants With Fasting Plasma TG &lt; 750 mg/dL at Month 3</title>
          <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Data were reported for evaluable participants.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>186.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>12.86</ci_lower_limit>
            <ci_upper_limit_na_comment>NA indicates that the upper limit of 95% CI was not estimable. The upper limit of the odds ratio estimate from the logistic regression model was &gt;999.999, and it was reported as NA per statistical reporting convention.</ci_upper_limit_na_comment>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3</title>
        <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
        <time_frame>Baseline to 3 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3</title>
          <description>The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>99.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>15.75</ci_lower_limit>
            <ci_upper_limit>631.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period</title>
        <description>Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.</description>
        <time_frame>Baseline to 12 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period</title>
          <description>Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period</title>
        <description>Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.</description>
        <time_frame>12 months</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period</title>
          <description>Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>events per participant per year</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.04" spread="4.28"/>
                    <measurement group_id="O2" value="2.73" spread="6.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6131</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52</title>
        <description>The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.</description>
        <time_frame>Baseline to Week 52</time_frame>
        <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Volanesorsen</title>
            <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52</title>
          <description>The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.</description>
          <population>The full analysis set included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.</population>
          <units>cubic centimeters (cm^3)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25" lower_limit="-150" upper_limit="100"/>
                    <measurement group_id="O2" value="113" lower_limit="-43" upper_limit="269"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1206</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>138</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-36</ci_lower_limit>
            <ci_upper_limit>312</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to approximately 65 weeks.</time_frame>
      <desc>The safety set included all randomized participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Volanesorsen</title>
          <description>Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.1)</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="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Drug-induced liver injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.1)</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="27" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site discolouration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site induration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site pallor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site warmth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site dryness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Injection site urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Creatinine renal clearance decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ionis Pharmaceuticals, Inc.</name_or_title>
      <organization>Ionis Pharmaceuticals, Inc.</organization>
      <phone>800-679-4747</phone>
      <email>patients@ionisph.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/NCT02211209
org study id: ISIS 304801-CS6
secondary id: 2014-002421-35
nct id: NCT02211209
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52
      weeks in participants with Familial Chylomicronemia Syndrome
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3
time frame: Baseline to 3 months
description: The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
measure: Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)
time frame: Baseline to an on-treatment assessment between Week 13 and Week 19
description: Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.
measure: Absolute Change From Baseline in Fasting TG at Month 3
time frame: Baseline to 3 months
description: The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
measure: Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3
time frame: Baseline to 3 months
description: The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter
measure: Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3
time frame: Baseline to 3 months
description: The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
measure: Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period
time frame: Baseline to 12 months
description: Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.
measure: Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period
time frame: 12 months
description: Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.
measure: Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52
time frame: Baseline to Week 52
description: The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.
arm group label: Placebo
arm group type: Placebo Comparator
description: Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.
arm group label: Volanesorsen
arm group type: Experimental
description: Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.
intervention type: Drug
intervention name: Volanesorsen
arm group label: Volanesorsen
other name: ISIS 304801
other name: ApoC-III
other name: Approach
other name: IONIS-APOCIIIRx
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Brazil
country: Canada
country: France
country: Germany
country: Hungary
country: Israel
country: Italy
country: Netherlands
country: South Africa
country: Spain
country: United Kingdom
country: United States
citation: Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944.
PMID: 31390500
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type I
mesh term: Syndrome
sharing ipd: No
participant flow: 
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reported events: 
certain agreements: 
point of contact: 