<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/NCT03028974</url>
  </required_header>
  <id_info>
    <org_study_id>SU-31136-2014-2019</org_study_id>
    <secondary_id>U19AI057229-11</secondary_id>
    <nct_id>NCT03028974</nct_id>
  </id_info>
  <brief_title>Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029)</brief_title>
  <official_title>Adaptive and Innate Immunity, Memory and Repertoire in Vaccination and Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to get a better understanding of the natural and adaptive immune&#xD;
      response to the flu virus and to compare the immune cell responses to FDA-licensed flu&#xD;
      vaccines in nasal mucosal cells and in blood.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study of healthy children and adults receive the current seasonal influenza&#xD;
      vaccine. The volunteers were enrolled into one of 7 groups over a 5-year period. Immunization&#xD;
      is administered; blood samples and NP swabs are collected at various time points based on&#xD;
      groups assigned.&#xD;
&#xD;
      Group A (LAIV4/annual return): Up to six 2-4 year old volunteers are given a quadrivalent&#xD;
      live, attenuated influenza vaccine (LAIV4). All participants in this group are asked to&#xD;
      return annually for flu immunization and blood samples on Day 0 and Day 7 post immunization.&#xD;
      Vaccine naive children returned 30 days later for a second immunization per standard of care.&#xD;
      This group was discontinued in year 3 due to Advisory Committee on Immunization Practices&#xD;
      (ACIP) recommendations against the use of LAIV.&#xD;
&#xD;
      Group B (LAIV4/ single year): Up to twenty 2-4 year old volunteers were given a quadrivalent&#xD;
      live, attenuated influenza vaccine (LAIV4). Volunteers will participate for a single year.&#xD;
      All participants in this group were immunized on Day 0. Blood samples were taken on on Day 0&#xD;
      and Day 7 post immunization. Vaccine naive children returned 30 days later for a second&#xD;
      immunization per standard of care. This group was discontinued in year 3 due to ACIP&#xD;
      recommendations against the use of LAIV.&#xD;
&#xD;
      Group C (LAIV4/NP swab group): Up to twenty 2-4 year old volunteers were given a quadrivalent&#xD;
      live, attenuated influenza vaccine (LAIV4). Nasopharyngeal samples (NP) swabs were collected&#xD;
      Day 1 and 21 and 28 post immunization. No blood was collected for this group. Vaccine naive&#xD;
      children returned 30 days later for a second immunization per standard of care. This group&#xD;
      was discontinued in year 3 due to ACIP recommendations against the use of LAIV.&#xD;
&#xD;
      Group D (IIV4/annual return): Up to six 6 month-23 month old (inclusive) volunteers are given&#xD;
      a quadrivalent inactivated influenza vaccine (IIV4). All participants in this group are asked&#xD;
      to return annually for flu immunization and blood samples on Day 0 and Day 7 post&#xD;
      immunization. Vaccine naive children returned 30 days later for a second immunization per&#xD;
      standard of care.&#xD;
&#xD;
      Group E (IIV4/single year): Up to twenty 6 month-23 month old (inclusive) volunteers were&#xD;
      given a quadrivalent inactivated influenza vaccine (IIV4). Volunteers participate for a&#xD;
      single year. All participants in this group were immunized on Day 0. Blood samples were taken&#xD;
      on on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a&#xD;
      second immunization per standard of care.&#xD;
&#xD;
      Group F (LAIV4/single year) Up to forty 9-13 year old (n= 20) and 18-49 year old (n= 20)&#xD;
      volunteers were given live, attenuated influenza vaccine (LAIV). Blood samples were collected&#xD;
      Days 0, 7, and 28 and NP swabs were collected Days 1 and 28. This group was discontinued in&#xD;
      year 3 due to ACIP recommendations against the use of LAIV.&#xD;
&#xD;
      Group G (IIV4/single year) Up to forty, 9-13 year old (n= 20) and 18-49 year old (n= 20)&#xD;
      volunteers were given a quadrivalent inactivated influenza vaccine (IIV4). Blood samples were&#xD;
      collected Day 0,7, and 28&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 17, 2014</start_date>
  <completion_date type="Actual">November 20, 2017</completion_date>
  <primary_completion_date type="Actual">November 20, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Count of Participants From Each Arm Who Received Influenza Vaccine</measure>
    <time_frame>Day 0 to 28-32 post immunization</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Count of Participants With Related Adverse Events</measure>
    <time_frame>Day 0 to 28-32 post-immunization</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Group A: 2-4 yo LAIV4 (Return)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: 2-4 yo LAIV4 (Single Yr)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants are given LAIV4/ FluMist® and participate for single year. For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C: 2-4 yo LAIV4 (Swab/Single Yr)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants are given LAIV4/ FluMist® and participate for single year. NP swabs are collected; no blood samples will be collected for this group. For children requiring 2 doses of vaccine, a second immunization will be given at least 28 days after Dose 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D: 6 - 23 mos old IIV4 (Return)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group E: 6 - 23 mos old IIV4 (Single Yr)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group G: 9-13/18-49 yo IIV4 (Single Yr)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fluzone®</intervention_name>
    <description>Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
    <arm_group_label>Group D: 6 - 23 mos old IIV4 (Return)</arm_group_label>
    <arm_group_label>Group E: 6 - 23 mos old IIV4 (Single Yr)</arm_group_label>
    <arm_group_label>Group G: 9-13/18-49 yo IIV4 (Single Yr)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>FluMist®</intervention_name>
    <description>FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
    <arm_group_label>Group A: 2-4 yo LAIV4 (Return)</arm_group_label>
    <arm_group_label>Group B: 2-4 yo LAIV4 (Single Yr)</arm_group_label>
    <arm_group_label>Group C: 2-4 yo LAIV4 (Swab/Single Yr)</arm_group_label>
    <arm_group_label>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Otherwise healthy, 6 mo-49 year-old volunteers.&#xD;
&#xD;
          2. Willing to complete the informed consent process (including assent for minors 7-17&#xD;
             years of age).&#xD;
&#xD;
          3. Availability for follow-up for the planned duration of the study.&#xD;
&#xD;
          4. For parents of children 6 months - 4 years of age: Willing to participate in the study&#xD;
             annually for up to 5 years (if yes, consider for annual return groups).&#xD;
&#xD;
          5. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.&#xD;
&#xD;
          6. Influenza vaccine-naive or only one prior season of flu immunization with IIV (does&#xD;
             not apply to Groups F and G).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior off-study vaccination with the current year's seasonal influenza vaccine&#xD;
&#xD;
          2. Receipt of LAIV in the prior season (does not apply to Groups F and G)&#xD;
&#xD;
          3. Received flu immunizations in 2 or more prior flu seasons (does not apply to Groups F&#xD;
             and G)&#xD;
&#xD;
          4. Allergy to egg or egg products, or to vaccine components, (including gentamicin,&#xD;
             gelatin, arginine or MSG if given LAIV4)&#xD;
&#xD;
          5. Life-threatening reactions to previous influenza vaccinations&#xD;
&#xD;
          6. Asthma in adults. Children aged 2 through 4 years who have asthma or who have had a&#xD;
             wheezing episode noted in the medical record within the past 12 months, or for whom&#xD;
             parents report that a health care provider stated that they had wheezing or asthma&#xD;
             within the last 12 months [If yes, not eligible for LAIV Groups A, B, C, &amp; F].&#xD;
&#xD;
          7. Active systemic or serious concurrent illness, including febrile illness on the day of&#xD;
             vaccination&#xD;
&#xD;
          8. History of immunodeficiency (including HIV infection)&#xD;
&#xD;
          9. For children or adolescents through 17 years of age,receiving aspirin therapy or&#xD;
             aspirin-containing products [If yes, not eligible for LAIV Groups A, B, C, and F].&#xD;
&#xD;
         10. Known or suspected impairment of immunologic function, including, but not limited to,&#xD;
             clinically significant liver disease, diabetes mellitus treated with insulin, moderate&#xD;
             to severe renal disease, or any other chronic disorder which, in the opinion of the&#xD;
             investigator, might jeopardize volunteer safety or compliance with the protocol.&#xD;
&#xD;
         11. Blood pressure &gt;150 systolic or &gt;95 diastolic at first study visit and the day of&#xD;
             vaccination (for children 12 yrs and older, and adults).&#xD;
&#xD;
         12. Hospitalization in the past year for congestive heart failure or emphysema.&#xD;
&#xD;
         13. Chronic Hepatitis B or C&#xD;
&#xD;
         14. Recent or current use of immunosuppressive medication, including systemic&#xD;
             glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in&#xD;
             all groups; inhaled steroid use is not permissible)&#xD;
&#xD;
         15. Participants in close contact with anyone who has a severely weakened immune system&#xD;
             and requires a protective environment. Exposure to such persons should be avoided for&#xD;
             7 days after receipt of LAIV. [If yes, may be ineligible for Groups A,B, C and F].&#xD;
&#xD;
         16. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors&#xD;
             such as breast cancer or prostate cancer with recurrence in the past year, and any&#xD;
             hematologic cancer such as leukemia).&#xD;
&#xD;
         17. Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive&#xD;
             medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion&#xD;
             of the investigator, might jeopardize volunteer safety or compliance with the protocol&#xD;
&#xD;
         18. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular&#xD;
             medical follow up or hospitalization during the preceding year&#xD;
&#xD;
         19. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet&#xD;
             agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox must be&#xD;
             reviewed by investigator to determine if this would affect the volunteer's safety.&#xD;
&#xD;
         20. Has taken an influenza antiviral medication within 48 hours prior to study vaccination&#xD;
             [If yes, not eligible for LAIV Groups A, B, C and F].&#xD;
&#xD;
         21. Receipt of blood or blood products within the past 6 months or planned used during the&#xD;
             study&#xD;
&#xD;
         22. Medical or psychiatric condition or occupational responsibilities that preclude&#xD;
             participant compliance with the protocol.&#xD;
&#xD;
         23. Receipt of inactivated vaccine 14 days prior to study enrollment, or planned&#xD;
             vaccinations prior to completion of last study visit&#xD;
&#xD;
         24. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned&#xD;
             vaccination prior to completion of last study visit&#xD;
&#xD;
         25. Need for allergy immunization (that cannot be postponed) during the study period&#xD;
&#xD;
         26. History of Guillain-Barre syndrome&#xD;
&#xD;
         27. Pregnant woman&#xD;
&#xD;
         28. Breastfeeding [If yes, not eligible for LAIV Group F]&#xD;
&#xD;
         29. Use of investigational agents within 30 days prior to enrollment or planned use during&#xD;
             the study&#xD;
&#xD;
         30. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or&#xD;
             planned donation prior to completion of the last visit&#xD;
&#xD;
         31. Any condition which, in the opinion of the investigator, might interfere with&#xD;
             volunteer safety, study objectives or the ability of the participant to understand or&#xD;
             comply with the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cornelia Dekker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Harry Greenberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Xiaosong He, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>November 20, 2018</results_first_submitted>
  <results_first_submitted_qc>November 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 14, 2018</results_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Cornelia L. Dekker</investigator_full_name>
    <investigator_title>Professor, Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Inactivated influenza vaccine</keyword>
  <keyword>Live, attenuated influenza vaccine</keyword>
  <keyword>Young children</keyword>
  <keyword>Adults</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 7, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT03028974/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants are presented only in the group in the year in which they received the vaccination. Planned Groups B and C did not enroll in years 2014-2018, Group A did not enroll in 2015-2018 and Group F did not enroll in years 2016-2018 due to LAIV not being recommended.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A: 2-4 yo LAIV4 (Return)</title>
          <description>Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="P2">
          <title>Group B: 2-4 yo LAIV4 (Single Year)</title>
          <description>Participants are given LAIV4/ FluMist® and participate for single year. For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="P3">
          <title>Group C: 2-4 yo LAIV4 (Swab/Single Yr)</title>
          <description>Participants are given LAIV4/ FluMist® and participate for single year. NP swabs are collected; no blood samples will be collected for this group. For children requiring 2 doses of vaccine, a second immunization will be given at least 28 days after Dose 1.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="P4">
          <title>Group D: 6 - 23 Mos Old IIV4 (Returning)</title>
          <description>Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="P5">
          <title>Group E: 6 - 23 Mos Old IIV4 (Single Yr)</title>
          <description>Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="P6">
          <title>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</title>
          <description>Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="P7">
          <title>Group G: 9-13/18-49 yo IIV4 (Single Yr)</title>
          <description>Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>2014-2015</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="11"/>
                <participants group_id="P7" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="11">2 participants did not continue to the next period.</participants>
                <participants group_id="P7" count="13">13 participants did not continue to the next period.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>2015-2016</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6">One participant joined from Group A, 2 new were enrolled.</participants>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="14">10 new participants were enrolled; 4 subjects switched from Group G.</participants>
                <participants group_id="P7" count="20">11 new participants were enrolled; 9 subjects switched from Group F.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6">3 participants did not continue to the next period. 1 Participant returned in period 4 (2017-2018).</participants>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="14">14 participants did not continue to the next period.</participants>
                <participants group_id="P7" count="20">20 participants did not continue to the next period.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>2016-2017</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4">1 new participant was enrolled.</participants>
                <participants group_id="P5" count="2">2 new participants were enrolled.</participants>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="18">18 new participants were enrolled.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2">2 participants did not continue to the next period</participants>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="18">18 participants did not continue to the next period.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>2017-2018</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="5">5 new participants were enrolled.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>In 2014, LAIV was not recommended in this age group.</population>
      <group_list>
        <group group_id="B1">
          <title>Group A: 2-4 yo LAIV4 (Return)</title>
          <description>Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="B2">
          <title>Group D: 6 - 23 Mos Old IIV4 (Return)</title>
          <description>Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="B3">
          <title>Group E: 6 - 23 Mos Old IIV4 (Single Yr)</title>
          <description>Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="B4">
          <title>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</title>
          <description>Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="B5">
          <title>Group G: 9-13/18-49 yo IIV4 (Single Yr)</title>
          <description>Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="2"/>
            <count group_id="B4" value="21"/>
            <count group_id="B5" value="47"/>
            <count group_id="B6" value="77"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" spread="0"/>
                    <measurement group_id="B2" value="1.5" spread="00.187"/>
                    <measurement group_id="B3" value="1" spread="0"/>
                    <measurement group_id="B4" value="20" spread="13.05"/>
                    <measurement group_id="B5" value="33.5" spread="1.48"/>
                    <measurement group_id="B6" value="21.1" spread="1.64"/>
                  </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="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="30"/>
                    <measurement group_id="B6" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="17"/>
                    <measurement group_id="B6" value="33"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="19"/>
                    <measurement group_id="B5" value="45"/>
                    <measurement group_id="B6" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="26"/>
                    <measurement group_id="B6" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="47"/>
                    <measurement group_id="B6" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Count of Participants From Each Arm Who Received Influenza Vaccine</title>
        <time_frame>Day 0 to 28-32 post immunization</time_frame>
        <population>Participants with available data at the respective timepoint are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: 2-4 yo LAIV4 (Return)</title>
            <description>Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
          </group>
          <group group_id="O2">
            <title>Group D: 6 - 23 Mos Old IIV4 (Returning)</title>
            <description>Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
          <group group_id="O3">
            <title>Group E: 6 - 23 Mos Old IIV4 (Single Yr)</title>
            <description>Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
          <group group_id="O4">
            <title>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</title>
            <description>Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
          </group>
          <group group_id="O5">
            <title>Group G: 9-13/18-49 yo IIV4 (Single Yr)</title>
            <description>Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants From Each Arm Who Received Influenza Vaccine</title>
          <population>Participants with available data at the respective timepoint are included in the analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="25"/>
                <count group_id="O5" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2014-2015</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="11"/>
                    <count group_id="O5" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O4" value="11"/>
                    <measurement group_id="O5" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2015-2016</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="14"/>
                    <count group_id="O5" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O4" value="14"/>
                    <measurement group_id="O5" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2016-2017</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="2"/>
                    <count group_id="O4" value="0"/>
                    <count group_id="O5" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O5" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2017-2018</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                    <count group_id="O5" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants With Related Adverse Events</title>
        <time_frame>Day 0 to 28-32 post-immunization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A: 2-4 yo LAIV4 (Return)</title>
            <description>Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
          </group>
          <group group_id="O2">
            <title>Group D: 6 - 23 Mos Old IIV4 (Return)</title>
            <description>Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
          <group group_id="O3">
            <title>Group E: 6 - 23 Mos Old IIV4 (Single Yr)</title>
            <description>Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
          <group group_id="O4">
            <title>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</title>
            <description>Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
          </group>
          <group group_id="O5">
            <title>Group G: 9-13/18-49 yo IIV4 (Single Yr)</title>
            <description>Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With Related Adverse Events</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="25"/>
                <count group_id="O5" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="7"/>
                    <measurement group_id="O5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 0 to 28-32 post-immunization</time_frame>
      <desc>Only related adverse events and related serious adverse events were collected.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group A: 2-4 yo LAIV4 (Return)</title>
          <description>Participants were given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization was given at Day 28-32 after Dose 1. All participants in this group was asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="E2">
          <title>Group D: 6 - 23 Mos Old IIV4 (Returning)</title>
          <description>Participants were given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization was given at Day 28-32 after Dose 1. Participants were asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="E3">
          <title>Group E: 6 - 23 Mos Old IIV4 (Single Yr)</title>
          <description>Participants were given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization was given at Day 28-32 after Dose 1.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
        <group group_id="E4">
          <title>Group F: 9-13/18-49 yo LAIV4 (Single Yr)</title>
          <description>Participants 9-13-year-old and 18-49-year-old were given LAIV4/ FluMist ®. Participants participated for a single year.&#xD;
FluMist®: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray</description>
        </group>
        <group group_id="E5">
          <title>Group G: 9-13/18-49 yo IIV4 (Single Yr)</title>
          <description>Participants 9-13-year-old and 18-49-year-old were given IIV4/ Fluzone® and participated for a single year.&#xD;
Fluzone®: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine</description>
        </group>
      </group_list>
      <serious_events>
        <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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="25"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mild Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Nasal mucous drainage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <description>Rash with erythema below injection site</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <description>Ecchymosis at phlebotomy site</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Post procedure bleeding</sub_title>
                <description>A small amount of blood noted on the swab when the NP sample was obtained.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="56"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The original design of this study was corrupted when the ACIP decided that LAIV administration was not recommended over concerns re: decreased immunogenicity and effectiveness.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Cornelia Dekker, MD</name_or_title>
      <organization>Stanford University</organization>
      <phone>650-724-4437</phone>
      <email>cdekker@stanford.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03028974
org study id: SU-31136-2014-2019
secondary id: U19AI057229-11
nct id: NCT03028974
lead sponsor: 
collaborator: 
has dmc: No
The purpose of the study is to get a better understanding of the natural and adaptive immune
      response to the flu virus and to compare the immune cell responses to FDA-licensed flu
      vaccines in nasal mucosal cells and in blood.
This is a study of healthy children and adults receive the current seasonal influenza
      vaccine. The volunteers were enrolled into one of 7 groups over a 5-year period. Immunization
      is administered; blood samples and NP swabs are collected at various time points based on
      groups assigned.

      Group A (LAIV4/annual return): Up to six 2-4 year old volunteers are given a quadrivalent
      live, attenuated influenza vaccine (LAIV4). All participants in this group are asked to
      return annually for flu immunization and blood samples on Day 0 and Day 7 post immunization.
      Vaccine naive children returned 30 days later for a second immunization per standard of care.
      This group was discontinued in year 3 due to Advisory Committee on Immunization Practices
      (ACIP) recommendations against the use of LAIV.

      Group B (LAIV4/ single year): Up to twenty 2-4 year old volunteers were given a quadrivalent
      live, attenuated influenza vaccine (LAIV4). Volunteers will participate for a single year.
      All participants in this group were immunized on Day 0. Blood samples were taken on on Day 0
      and Day 7 post immunization. Vaccine naive children returned 30 days later for a second
      immunization per standard of care. This group was discontinued in year 3 due to ACIP
      recommendations against the use of LAIV.

      Group C (LAIV4/NP swab group): Up to twenty 2-4 year old volunteers were given a quadrivalent
      live, attenuated influenza vaccine (LAIV4). Nasopharyngeal samples (NP) swabs were collected
      Day 1 and 21 and 28 post immunization. No blood was collected for this group. Vaccine naive
      children returned 30 days later for a second immunization per standard of care. This group
      was discontinued in year 3 due to ACIP recommendations against the use of LAIV.

      Group D (IIV4/annual return): Up to six 6 month-23 month old (inclusive) volunteers are given
      a quadrivalent inactivated influenza vaccine (IIV4). All participants in this group are asked
      to return annually for flu immunization and blood samples on Day 0 and Day 7 post
      immunization. Vaccine naive children returned 30 days later for a second immunization per
      standard of care.

      Group E (IIV4/single year): Up to twenty 6 month-23 month old (inclusive) volunteers were
      given a quadrivalent inactivated influenza vaccine (IIV4). Volunteers participate for a
      single year. All participants in this group were immunized on Day 0. Blood samples were taken
      on on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a
      second immunization per standard of care.

      Group F (LAIV4/single year) Up to forty 9-13 year old (n= 20) and 18-49 year old (n= 20)
      volunteers were given live, attenuated influenza vaccine (LAIV). Blood samples were collected
      Days 0, 7, and 28 and NP swabs were collected Days 1 and 28. This group was discontinued in
      year 3 due to ACIP recommendations against the use of LAIV.

      Group G (IIV4/single year) Up to forty, 9-13 year old (n= 20) and 18-49 year old (n= 20)
      volunteers were given a quadrivalent inactivated influenza vaccine (IIV4). Blood samples were
      collected Day 0,7, and 28
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Count of Participants From Each Arm Who Received Influenza Vaccine
time frame: Day 0 to 28-32 post immunization
measure: Count of Participants With Related Adverse Events
time frame: Day 0 to 28-32 post-immunization
arm group label: Group A: 2-4 yo LAIV4 (Return)
arm group type: Other
description: Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.
arm group label: Group B: 2-4 yo LAIV4 (Single Yr)
arm group type: Other
description: Participants are given LAIV4/ FluMist® and participate for single year. For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1.
arm group label: Group C: 2-4 yo LAIV4 (Swab/Single Yr)
arm group type: Other
description: Participants are given LAIV4/ FluMist® and participate for single year. NP swabs are collected; no blood samples will be collected for this group. For children requiring 2 doses of vaccine, a second immunization will be given at least 28 days after Dose 1.
arm group label: Group D: 6 - 23 mos old IIV4 (Return)
arm group type: Other
description: Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.
arm group label: Group E: 6 - 23 mos old IIV4 (Single Yr)
arm group type: Other
description: Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.
arm group label: Group F: 9-13/18-49 yo LAIV4 (Single Yr)
arm group type: Other
description: Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.
arm group label: Group G: 9-13/18-49 yo IIV4 (Single Yr)
arm group type: Other
description: Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.
intervention type: Biological
intervention name: Fluzone®
description: Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine
arm group label: Group D: 6 - 23 mos old IIV4 (Return)
arm group label: Group E: 6 - 23 mos old IIV4 (Single Yr)
arm group label: Group G: 9-13/18-49 yo IIV4 (Single Yr)
intervention type: Biological
intervention name: FluMist®
description: FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray
arm group label: Group A: 2-4 yo LAIV4 (Return)
arm group label: Group B: 2-4 yo LAIV4 (Single Yr)
arm group label: Group C: 2-4 yo LAIV4 (Swab/Single Yr)
arm group label: Group F: 9-13/18-49 yo LAIV4 (Single Yr)
criteria: 
gender: All
minimum age: 6 Months
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cornelia Dekker, MD
role: Principal Investigator
affiliation: Stanford University
last name: Harry Greenberg, MD
role: Principal Investigator
affiliation: Stanford University
last name: Xiaosong He, PhD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Cornelia L. Dekker
investigator title: Professor, Pediatrics
mesh term: Influenza, Human
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The original design of this study was corrupted when the ACIP decided that LAIV administration was not recommended over concerns re: decreased immunogenicity and effectiveness.
point of contact: 