<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/NCT03771963</url>
  </required_header>
  <id_info>
    <org_study_id>DEN-307</org_study_id>
    <secondary_id>U1111-1222-2812</secondary_id>
    <nct_id>NCT03771963</nct_id>
  </id_info>
  <brief_title>Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) at the End of Shelf Life in Healthy Adults</brief_title>
  <official_title>An Open-Label, Phase 3 Trial to Investigate the Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) at the End of Shelf Life in Healthy Adults in Non-Endemic Country(Ies) for Dengue</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and immune response of a naturally aged&#xD;
      lot of tetravalent dengue vaccine (TDV) in healthy participants, aged 18 to 60 years, in&#xD;
      non-endemic country(ies) for dengue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The vaccine being tested in this study is tetravalent dengue vaccine (TDV). The primary&#xD;
      objective of this study is to evaluate the immune response and safety of a naturally aged&#xD;
      (&gt;12 months stored at 2°C to 8°C) lot of TDV in a healthy adult population in country(ies)&#xD;
      non-endemic for dengue. The assessment of a naturally aged lot of TDV in this clinical trial&#xD;
      will provide an important contribution to data on TDV stability throughout the shelf life of&#xD;
      the product.&#xD;
&#xD;
      The study will enroll approximately 200 participants. Participants will be enrolled to the&#xD;
      one treatment group:&#xD;
&#xD;
      Tetravalent Dengue Vaccine (TDV)&#xD;
&#xD;
      All participants will receive subcutaneous (SC) injection on Day 1 (Month 0) and Day 90&#xD;
      (Month 3).&#xD;
&#xD;
      This multi-center trial will be conducted in the United States. The overall time to&#xD;
      participate in this study is 9 months. Participants will make multiple visits to the clinic&#xD;
      including a final visit at Day 270 (Month 9).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2019</start_date>
  <completion_date type="Actual">March 13, 2020</completion_date>
  <primary_completion_date type="Actual">October 14, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120</measure>
    <time_frame>One month post second dose (Day 120)</time_frame>
    <description>GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3, and DENV-4.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seropositivity Rates for Each of the 4 Dengue Serotypes at Days 120 and 270</measure>
    <time_frame>One month and six months post second dose (Days 120 and 270)</time_frame>
    <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at Days 120 and 270</measure>
    <time_frame>One month and six months post second dose (Days 120 and 270)</time_frame>
    <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity for multiple dengue serotypes was summarized in the following categories: tetravalent and at least trivalent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270</measure>
    <time_frame>Six months post second dose (Day 270)</time_frame>
    <description>GMTs of neutralizing antibodies were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity</measure>
    <time_frame>Up to 7 days (Day of vaccination + 6 subsequent days) after each of the vaccination</time_frame>
    <description>Solicited local adverse events (AEs) [at injection site] were collected by participants using diary cards within 7 days after each vaccination and included injection site pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], injection site erythema [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)] and injection site swelling [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)]. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity</measure>
    <time_frame>Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination</time_frame>
    <description>Solicited systemic AEs were collected by participants using diary cards within 14 days after each vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4°F). Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Any Unsolicited Adverse Events Following Each Vaccination</measure>
    <time_frame>Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days)</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Serious Adverse Events (SAEs)</measure>
    <time_frame>From first vaccination (Day 1) through end of study (Day 270)</time_frame>
    <description>An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, leads to a congenital anomaly / birth defect in the offspring of a participant, or is an important medical event which may require intervention to prevent the items listed above or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Medically Attended Adverse Events (MAAEs)</measure>
    <time_frame>From first vaccination (Day 1) through end of study (Day 270)</time_frame>
    <description>MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Dengue Fever</condition>
  <arm_group>
    <arm_group_label>Tetravalent Dengue Vaccine (TDV)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tetravalent Dengue Vaccine (TDV)</intervention_name>
    <description>TDV SC injection.</description>
    <arm_group_label>Tetravalent Dengue Vaccine (TDV)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants who are in good health at the time of entry into the trial as determined&#xD;
             by medical history, physical examination (including vital signs), and the clinical&#xD;
             judgment of the investigator.&#xD;
&#xD;
          2. Participants who sign and date a written informed consent form and any required&#xD;
             privacy authorization prior to the initiation of any trial procedures, after the&#xD;
             nature of the trial has been explained according to local regulatory requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants with a clinically significant active infection (as assessed by the&#xD;
             investigator) or body temperature ≥38°C (≥100.4°F) within 3 days of the intended date&#xD;
             of vaccine administration&#xD;
&#xD;
          2. Known or suspected impairment/alteration of immune function, including:&#xD;
&#xD;
               1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or&#xD;
                  ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1&#xD;
                  (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).&#xD;
&#xD;
               2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks&#xD;
                  and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day&#xD;
                  1 (Month 0).&#xD;
&#xD;
               3. Administration of immunoglobulins and/or any blood products within the 3 months&#xD;
                  prior to Day 1 (Month 0) or planned administration during the trial.&#xD;
&#xD;
               4. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).&#xD;
&#xD;
               5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy&#xD;
                  within 6 months prior to Day 1 (Month 0).&#xD;
&#xD;
               6. Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.&#xD;
&#xD;
               7. Hepatitis C virus infection.&#xD;
&#xD;
               8. Genetic immunodeficiency.&#xD;
&#xD;
          3. With Body Mass Index (BMI) greater than or equal to 35 kg/m^2(=weight in kg/height in&#xD;
             meters^2).&#xD;
&#xD;
          4. Participants who have known hypersensitivity or allergy to any of the vaccine&#xD;
             components.&#xD;
&#xD;
          5. Previous and planned vaccination (during the trial conduct), against any flavivirus&#xD;
             including dengue, Yellow Fever (YF), Japanese Encephalitis (JE) viruses or tick-borne&#xD;
             encephalitis.&#xD;
&#xD;
          6. Previous participation in any clinical trial of a dengue or other flavivirus (e.g.,&#xD;
             West Nile [WN] virus) candidate vaccine, except for participants who received placebo&#xD;
             in those trials.&#xD;
&#xD;
          7. With a current or previous infection with a flavivirus such as dengue, Zika, YF, JE,&#xD;
             WN fever, tick-borne encephalitis or Murray Valley encephalitis and participants with&#xD;
             a history of prolonged (≥1 year) habitation in a dengue endemic area.&#xD;
&#xD;
          8. Participants with any history of progressive or severe neurologic disorder, seizure&#xD;
             disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).&#xD;
&#xD;
          9. Participants with history of substance or alcohol abuse within the past 2 years.&#xD;
&#xD;
         10. Participants who have any serious chronic or progressive disease according to judgment&#xD;
             of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or&#xD;
             hepatic disease).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anaheim Clinical Trials, LLC</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hutchinson Clinic</name>
      <address>
        <city>Hutchinson</city>
        <state>Kansas</state>
        <zip>67502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <results_first_submitted>May 11, 2021</results_first_submitted>
  <results_first_submitted_qc>May 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 7, 2021</results_first_posted>
  <disposition_first_submitted>October 12, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>October 12, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 19, 2020</disposition_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Live Attenuated Tetravalent Dengue Vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dengue</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03771963/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03771963/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 2 investigative sites in the United States from 28 March 2019 to 13 March 2020.</recruitment_details>
      <pre_assignment_details>Healthy participants were enrolled in this study to receive Tetravalent Dengue Vaccine (TDV) on Days 1 and 90.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tetravalent Dengue Vaccine (TDV)</title>
          <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="200"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="168"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal of Consent</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine.</population>
      <group_list>
        <group group_id="B1">
          <title>Tetravalent Dengue Vaccine (TDV)</title>
          <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.27" spread="12.035"/>
                  </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="101"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="136"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="170.72" spread="9.330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80.23" spread="15.220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <description>BMI= weight (kg)/[height (m)^2]</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.45" spread="4.248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120</title>
        <description>GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3, and DENV-4.</description>
        <time_frame>One month post second dose (Day 120)</time_frame>
        <population>Per-protocol Set (PPS) excludes all participants seropositive for dengue virus at Baseline and includes all participants in the Full Analysis Set (FAS- who received at least 1 dose of trial vaccine with valid pre-dose and post-dose measurement for immunogenicity assessment) who have no major protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120</title>
          <description>GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3, and DENV-4.</description>
          <population>Per-protocol Set (PPS) excludes all participants seropositive for dengue virus at Baseline and includes all participants in the Full Analysis Set (FAS- who received at least 1 dose of trial vaccine with valid pre-dose and post-dose measurement for immunogenicity assessment) who have no major protocol violations, with data available for analysis.</population>
          <units>titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="132"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DENV-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="557.4" lower_limit="417.0" upper_limit="744.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2047.4" lower_limit="1739.7" upper_limit="2409.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="131.8" lower_limit="105.0" upper_limit="165.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.6" lower_limit="97.7" upper_limit="146.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Seropositivity Rates for Each of the 4 Dengue Serotypes at Days 120 and 270</title>
        <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.</description>
        <time_frame>One month and six months post second dose (Days 120 and 270)</time_frame>
        <population>The PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations. Number analyzed is the number of participants with data available for analysis at the given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Seropositivity Rates for Each of the 4 Dengue Serotypes at Days 120 and 270</title>
          <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.</description>
          <population>The PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations. Number analyzed is the number of participants with data available for analysis at the given time point.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="139"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 120: DENV-1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.2" lower_limit="95.9" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 120: DENV-2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="97.2" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 120: DENV-3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.7" lower_limit="93.5" upper_limit="99.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 120: DENV-4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.2" lower_limit="95.9" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: DENV-1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.0" lower_limit="92.5" upper_limit="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: DENV-2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.5" lower_limit="94.7" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: DENV-3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.7" lower_limit="78.6" upper_limit="91.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: DENV-4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.5" lower_limit="79.5" upper_limit="91.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at Days 120 and 270</title>
        <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity for multiple dengue serotypes was summarized in the following categories: tetravalent and at least trivalent.</description>
        <time_frame>One month and six months post second dose (Days 120 and 270)</time_frame>
        <population>The PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations. Number analyzed is the number of participants with data available for analysis at the given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at Days 120 and 270</title>
          <description>Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity for multiple dengue serotypes was summarized in the following categories: tetravalent and at least trivalent.</description>
          <population>The PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations. Number analyzed is the number of participants with data available for analysis at the given time point.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="139"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 120: At Least Trivalent</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.2" lower_limit="95.9" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 120: Tetravalent</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.0" lower_limit="92.4" upper_limit="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: At Least Trivalent</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.0" lower_limit="84.8" upper_limit="95.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 270: Tetravalent</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.9" lower_limit="71.0" upper_limit="85.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270</title>
        <description>GMTs of neutralizing antibodies were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.</description>
        <time_frame>Six months post second dose (Day 270)</time_frame>
        <population>PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270</title>
          <description>GMTs of neutralizing antibodies were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.</description>
          <population>PPS excludes all participants seropositive for dengue virus at Baseline and includes all participants in the FAS who have no major protocol violations, with data available for analysis.</population>
          <units>titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DENV-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="311.6" lower_limit="222.8" upper_limit="435.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1170.6" lower_limit="953.9" upper_limit="1436.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.0" lower_limit="48.4" upper_limit="82.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENV-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.6" lower_limit="44.2" upper_limit="75.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity</title>
        <description>Solicited local adverse events (AEs) [at injection site] were collected by participants using diary cards within 7 days after each vaccination and included injection site pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], injection site erythema [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)] and injection site swelling [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)]. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
        <time_frame>Up to 7 days (Day of vaccination + 6 subsequent days) after each of the vaccination</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity</title>
          <description>Solicited local adverse events (AEs) [at injection site] were collected by participants using diary cards within 7 days after each vaccination and included injection site pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], injection site erythema [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)] and injection site swelling [Grade 0 (&lt;25 mm), 1 (25 - ≤ 50 mm), 2 (&gt;50 - ≤ 100 mm), 3 (&gt; 100 mm)]. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
          <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Vaccination, Any Solicited Local AEs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Pain: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Pain: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Pain: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Pain: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Erythema: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Erythema: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Erythema: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Swelling: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Swelling: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Any Solicited Local AEs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Pain: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Pain: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Pain: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Pain: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Erythema: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Erythema: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Swelling: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Swelling: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity</title>
        <description>Solicited systemic AEs were collected by participants using diary cards within 14 days after each vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4°F). Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
        <time_frame>Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity</title>
          <description>Solicited systemic AEs were collected by participants using diary cards within 14 days after each vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4°F). Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.</description>
          <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Vaccination, Any Solicited Systemic Local AEs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Headache: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Headache: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Headache: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Headache: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Myalgia: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Myalgia: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Myalgia: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Myalgia: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Asthenia: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Asthenia: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Asthenia: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Asthenia: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Malaise: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Malaise: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Malaise: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Malaise: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="192"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Fever: Any</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="189"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Fever: 38.0-&lt;38.5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="189"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After First Vaccination, Fever: 38.5-&lt;39.0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="189"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Any Solicited Systemic Local AEs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Headache: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Headache: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Headache: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Headache: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Myalgia: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Myalgia: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Myalgia: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Myalgia: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Asthenia: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Asthenia: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Asthenia: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Asthenia: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Malaise: Any Severity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Malaise: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Malaise: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Malaise: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="167"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Fever: Any</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="166"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Fever: 38.0-&lt;38.5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="166"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination, Fever: 38.5-&lt;39.0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="166"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Any Unsolicited Adverse Events Following Each Vaccination</title>
        <description>An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.</description>
        <time_frame>Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days)</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Any Unsolicited Adverse Events Following Each Vaccination</title>
          <description>An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.</description>
          <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine. Number analyzed is the number of participants with data available for the specific category.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Vaccination</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Second Vaccination</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="176"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Serious Adverse Events (SAEs)</title>
        <description>An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, leads to a congenital anomaly / birth defect in the offspring of a participant, or is an important medical event which may require intervention to prevent the items listed above or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.</description>
        <time_frame>From first vaccination (Day 1) through end of study (Day 270)</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Serious Adverse Events (SAEs)</title>
          <description>An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, leads to a congenital anomaly / birth defect in the offspring of a participant, or is an important medical event which may require intervention to prevent the items listed above or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.</description>
          <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Medically Attended Adverse Events (MAAEs)</title>
        <description>MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.</description>
        <time_frame>From first vaccination (Day 1) through end of study (Day 270)</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine.</population>
        <group_list>
          <group group_id="O1">
            <title>Tetravalent Dengue Vaccine (TDV)</title>
            <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Medically Attended Adverse Events (MAAEs)</title>
          <description>MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.</description>
          <population>Safety Set included all participants who received at least 1 dose of TDV trial vaccine.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All-cause mortality and Serious adverse events: From first vaccination (Day 1) through end of study (Day 270). Other (Non-serious) adverse events: Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days).</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tetravalent Dengue Vaccine (TDV)</title>
          <description>TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</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="200"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="200"/>
              </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>The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>TrialDisclosures@takeda.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/NCT03771963
org study id: DEN-307
secondary id: U1111-1222-2812
nct id: NCT03771963
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and immune response of a naturally aged
      lot of tetravalent dengue vaccine (TDV) in healthy participants, aged 18 to 60 years, in
      non-endemic country(ies) for dengue.
The vaccine being tested in this study is tetravalent dengue vaccine (TDV). The primary
      objective of this study is to evaluate the immune response and safety of a naturally aged
      (>12 months stored at 2°C to 8°C) lot of TDV in a healthy adult population in country(ies)
      non-endemic for dengue. The assessment of a naturally aged lot of TDV in this clinical trial
      will provide an important contribution to data on TDV stability throughout the shelf life of
      the product.

      The study will enroll approximately 200 participants. Participants will be enrolled to the
      one treatment group:

      Tetravalent Dengue Vaccine (TDV)

      All participants will receive subcutaneous (SC) injection on Day 1 (Month 0) and Day 90
      (Month 3).

      This multi-center trial will be conducted in the United States. The overall time to
      participate in this study is 9 months. Participants will make multiple visits to the clinic
      including a final visit at Day 270 (Month 9).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120
time frame: One month post second dose (Day 120)
description: GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3, and DENV-4.
measure: Seropositivity Rates for Each of the 4 Dengue Serotypes at Days 120 and 270
time frame: One month and six months post second dose (Days 120 and 270)
description: Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
measure: Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at Days 120 and 270
time frame: One month and six months post second dose (Days 120 and 270)
description: Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity for multiple dengue serotypes was summarized in the following categories: tetravalent and at least trivalent.
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270
time frame: Six months post second dose (Day 270)
description: GMTs of neutralizing antibodies were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
measure: Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity
time frame: Up to 7 days (Day of vaccination + 6 subsequent days) after each of the vaccination
description: Solicited local adverse events (AEs) [at injection site] were collected by participants using diary cards within 7 days after each vaccination and included injection site pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], injection site erythema [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)] and injection site swelling [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)]. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.
measure: Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity
time frame: Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination
description: Solicited systemic AEs were collected by participants using diary cards within 14 days after each vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4°F). Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.
measure: Percentage of Participants With Any Unsolicited Adverse Events Following Each Vaccination
time frame: Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days)
description: An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.
measure: Percentage of Participants With Serious Adverse Events (SAEs)
time frame: From first vaccination (Day 1) through end of study (Day 270)
description: An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, leads to a congenital anomaly / birth defect in the offspring of a participant, or is an important medical event which may require intervention to prevent the items listed above or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.
measure: Percentage of Participants With Medically Attended Adverse Events (MAAEs)
time frame: From first vaccination (Day 1) through end of study (Day 270)
description: MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.
arm group label: Tetravalent Dengue Vaccine (TDV)
arm group type: Experimental
description: TDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).
intervention type: Biological
intervention name: Tetravalent Dengue Vaccine (TDV)
description: TDV SC injection.
arm group label: Tetravalent Dengue Vaccine (TDV)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dengue
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 