<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/NCT02967393</url>
  </required_header>
  <id_info>
    <org_study_id>IIV4/LAIV4/CDC</org_study_id>
    <nct_id>NCT02967393</nct_id>
  </id_info>
  <brief_title>Influenza Vaccine Feasibility Study in Children With Persistent Asthma</brief_title>
  <official_title>Feasibility Study to Assess the Safety of Quadrivalent, Live Attenuated Influenza Vaccine (LAIV4) Versus Quadrivalent Inactivated Influenza Vaccine (IIV4) in Children Aged 5-11 Years With Persistent Asthma of Varied Severity (Cell Culture Quadrivalent IIV Used as Surrogate for LAIV4)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to note whether a larger safety study using quadrivalent live&#xD;
      attenuated influenza vaccine (LAIV4) versus quadrivalent inactivated influenza vaccine&#xD;
      (IIV4)(FLUARIX®), would be feasible in children with persistent asthma. Half of the patients&#xD;
      in this study will receive the FLUARIX® influenza vaccine, while the other half will receive&#xD;
      a cell cultured quadrivalent inactivated influenza vaccine (ccIIV4)(Flucelvax®) being used as&#xD;
      a surrogate for LAIV4.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The association of an increased risk in wheezing following receipt of a live-attenuated&#xD;
      influenza vaccine in children at least 2 years of age with a prior history of asthma or&#xD;
      wheeze remains unclear.&#xD;
&#xD;
      The Centers for Disease Control (CDC) and Prevention's Clinical Immunization Safety&#xD;
      Assessment (CISA) planned to address a data safety gap regarding use of LAIV4 vaccine in&#xD;
      children with asthma by conducting a 3-site randomized, non-inferiority prospective study.&#xD;
      The main goal was to compare the safety of LAIV4 versus IIV4 in children 5-11 years with&#xD;
      persistent asthma during the 2016-2017 influenza season. CDC and the CISA study sites&#xD;
      developed a protocol and associated materials, and were poised to begin enrollment early&#xD;
      during the 2016-2017 influenza season. However, after the June 22, 2016 Advisory Committee on&#xD;
      Immunization Practices (ACIP) vote recommending against use of LAIV4 during the 2016-2017&#xD;
      influenza season, CDC and study investigators decided to defer implementing a study using&#xD;
      LAIV4 during the 2016-2017 influenza season. Investigators will reconsider initiating this&#xD;
      study during the 2017-2018 influenza season if ACIP votes to reinstate LAIV4 use or new data&#xD;
      become available; ACIP makes recommendations annually.&#xD;
&#xD;
      The planned LAIV4 study had unique features in its design that previously had not been&#xD;
      implemented in vaccine safety studies, including: 1) enrolling a substantial proportion of&#xD;
      children with moderate-severe asthma 2) using digital peak flow meters and 3) collecting&#xD;
      clinical data through multiple, complementary, measures for 42 days after vaccination. To&#xD;
      capitalize on progress made during development of the study protocol and associated documents&#xD;
      and procedures, CISA is proposing to carry out a study at the three sites to assess the&#xD;
      feasibility of recruiting, enrolling, retaining, and collecting clinical data on children&#xD;
      5-11 years with persistent asthma of varied levels of severity in an influenza vaccine safety&#xD;
      study. Findings from this proposed feasibility study will facilitate improving the LAIV4&#xD;
      study in the future if it goes forward through the CISA Project or in another venue. In&#xD;
      2016-2017 season, FDA approved a new influenza vaccine for use in persons aged 4 years and&#xD;
      older, Flucelvax® Quadrivalent (ccIIV4); ACIP incorporated this vaccine into its&#xD;
      recommendations for the 2016-2017 influenza season. Therefore ccIIV4 will be used in place of&#xD;
      LAIV4 for this feasibility study. There is no evidence that Flucelvax® increases the risk of&#xD;
      wheezing in asthmatic children. The feasibility study also offers an opportunity to gain some&#xD;
      additional descriptive safety data for this new vaccine in asthmatic children.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 10, 2016</start_date>
  <completion_date type="Actual">February 1, 2017</completion_date>
  <primary_completion_date type="Actual">February 1, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1.</measure>
    <time_frame>15 days</time_frame>
    <description>Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data</measure>
    <time_frame>Day 16 to 43</time_frame>
    <description>Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements</measure>
    <time_frame>15 days</time_frame>
    <description>Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42</measure>
    <time_frame>Day 42</time_frame>
    <description>Parent will perform and document the digital peak flow for Day 42</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings</measure>
    <time_frame>15 days</time_frame>
    <description>Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data</measure>
    <time_frame>Day 3 to 6</time_frame>
    <description>Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data.</measure>
    <time_frame>Day 8-10</time_frame>
    <description>Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data</measure>
    <time_frame>Day 14 to 17</time_frame>
    <description>Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data.</measure>
    <time_frame>Day 29-31</time_frame>
    <description>Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents That Respond to Day 44 Call</measure>
    <time_frame>Day 44-47</time_frame>
    <description>Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey</measure>
    <time_frame>42 days</time_frame>
    <description>Parent of each participant will be asked to complete a at the end of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severe Local Reactogenicity Events During the 14 Days Post-vaccination</measure>
    <time_frame>14 days</time_frame>
    <description>Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination</measure>
    <time_frame>14 days</time_frame>
    <description>Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unsolicited and Severe Adverse Events</measure>
    <time_frame>42 days</time_frame>
    <description>The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Asthma Exacerbations Requiring Steroids</measure>
    <time_frame>42 days</time_frame>
    <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number Participants With Asthma Exacerbations Requiring Medical Attention</measure>
    <time_frame>42 days</time_frame>
    <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Asthmatic</condition>
  <arm_group>
    <arm_group_label>IIV4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.5 mL intramuscular injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cc IIV4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.5 mL intramuscular injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ccIIV4</intervention_name>
    <arm_group_label>cc IIV4</arm_group_label>
    <other_name>Flucelvax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IIV4</intervention_name>
    <arm_group_label>IIV4</arm_group_label>
    <other_name>Fluarix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children between 5-11 years of age, inclusive, at enrollment.&#xD;
&#xD;
          -  Participant must have a current diagnosis of persistent asthma.&#xD;
&#xD;
          -  Parent/legal guardian must provide written informed consent and subject must provide&#xD;
             assent as appropriate for age prior to initiation of study procedures and according to&#xD;
             local Institutional Review Board (IRB) requirement.&#xD;
&#xD;
          -  Parent/legal guardian and subject must be willing and able to comply with planned&#xD;
             study procedures and be available for all study visits.&#xD;
&#xD;
          -  Children aged 5-8 years must have received at least 2 doses of seasonal trivalent or&#xD;
             quadrivalent influenza vaccine prior to the current influenza season. Children 9-11&#xD;
             years must have received at least 1 dose of seasonal trivalent or quadrivalent&#xD;
             influenza vaccine prior to the current influenza season.&#xD;
&#xD;
          -  Is in good health, other than their asthma, as determined by medical history and&#xD;
             targeted physical examination based on medical history.&#xD;
&#xD;
          -  English or Spanish literate.&#xD;
&#xD;
          -  Intention of being available for entire study period and complete all relevant study&#xD;
             procedures, including follow-up phone calls and collection of information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute illness and/or a reported oral temperature of ≥ 100.4°F within 72 hours prior to&#xD;
             enrollment (this may result in a temporary delay of vaccination.&#xD;
&#xD;
          -  Use of antipyretic medication during the preceding 24 hours that might mask a fever&#xD;
             (temporary deferral).&#xD;
&#xD;
          -  History of a severe allergic reaction (e.g., anaphylaxis) to any component of study&#xD;
             influenza vaccines or a known allergy to eggs.&#xD;
&#xD;
          -  Receipt of any licensed vaccine within 14 days (for inactivated vaccines) or 28 days&#xD;
             (for live vaccines) prior to vaccination or planned receipt of any licensed vaccine&#xD;
             within 42 days after vaccination.&#xD;
&#xD;
          -  Receipt of current year's licensed influenza vaccine.&#xD;
&#xD;
          -  Received an investigational agent (licensed or unlicensed vaccine, drug, biologic,&#xD;
             device, blood product, or medication) in the 28 days prior to enrollment or planned&#xD;
             receipt before 42 days after vaccination.&#xD;
&#xD;
          -  Has immunosuppression as a result of an underlying illness or treatment, or use of&#xD;
             anticancer chemotherapy or radiation therapy within the preceding 36 months.&#xD;
&#xD;
          -  Has taken ≥ 20mg/day of prednisone or its equivalent, for 14 days or more within the&#xD;
             past 28 days.&#xD;
&#xD;
          -  Has know active neoplasm or a history of any hematologic malignancy.&#xD;
&#xD;
          -  Has had a previous exacerbation of their asthma symptoms requiring systemic steroids&#xD;
             within the prior 28 days, or has had a life-threatening exacerbation of asthma in the&#xD;
             past two years (e.g. hypoxic seizure, mechanical ventilation).&#xD;
&#xD;
          -  History of Guillian-Barre syndrome within 6 weeks of previous influenza vaccination.&#xD;
&#xD;
          -  Has any condition that, in the opinion of the investigator, would interfere with the&#xD;
             evaluation of the responses or would place the participant at unacceptable risk of&#xD;
             injury.&#xD;
&#xD;
          -  Has any diagnosis, current or past, of schizophrenia, bipolar disease, or other major&#xD;
             psychiatric disorder.&#xD;
&#xD;
          -  Currently taking aspirin or aspirin-containing products.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>11 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathryn M Edwards, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt Vaccine Research Program</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centers for Disease Control and Prevention</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Clinical Vaccine Unit</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Vaccine Research Program</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>October 31, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>January 9, 2018</results_first_submitted>
  <results_first_submitted_qc>March 22, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 23, 2018</results_first_posted>
  <last_update_submitted>March 22, 2018</last_update_submitted>
  <last_update_submitted_qc>March 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Kathryn Edwards</investigator_full_name>
    <investigator_title>Sarah H. Sell and Cornelius Vanderbilt Professor of Pediatrics</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Asthma</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 19, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02967393/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Feasibility Measures are done by the parent/guardian of the participants. Feasibility Measure data will be reported as a single group.&#xD;
Participant data (vaccine data) will be reported by the type of vaccination received.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>ccIIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
        </group>
        <group group_id="P2">
          <title>IIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ccIIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
        </group>
        <group group_id="B2">
          <title>IIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_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="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="24"/>
                  </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="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="36"/>
                  </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_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_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="0"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </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_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="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1.</title>
        <description>Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.</description>
        <time_frame>15 days</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Parents</title>
            <description>Parents of participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1.</title>
          <description>Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data</title>
        <description>Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.</description>
        <time_frame>Day 16 to 43</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data</title>
          <description>Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements</title>
        <description>Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.</description>
        <time_frame>15 days</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements</title>
          <description>Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42</title>
        <description>Parent will perform and document the digital peak flow for Day 42</description>
        <time_frame>Day 42</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received.. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42</title>
          <description>Parent will perform and document the digital peak flow for Day 42</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received.. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings</title>
        <description>Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.</description>
        <time_frame>15 days</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings</title>
          <description>Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data</title>
        <description>Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data</description>
        <time_frame>Day 3 to 6</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data</title>
          <description>Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data.</title>
        <description>Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.</description>
        <time_frame>Day 8-10</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data.</title>
          <description>Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data</title>
        <description>Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data</description>
        <time_frame>Day 14 to 17</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data</title>
          <description>Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data.</title>
        <description>Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.</description>
        <time_frame>Day 29-31</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data.</title>
          <description>Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents That Respond to Day 44 Call</title>
        <description>Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.</description>
        <time_frame>Day 44-47</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents That Respond to Day 44 Call</title>
          <description>Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey</title>
        <description>Parent of each participant will be asked to complete a at the end of the study</description>
        <time_frame>42 days</time_frame>
        <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants from both arms</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey</title>
          <description>Parent of each participant will be asked to complete a at the end of the study</description>
          <population>Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Local Reactogenicity Events During the 14 Days Post-vaccination</title>
        <description>Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
        <time_frame>14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ccIIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
          </group>
          <group group_id="O2">
            <title>IIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Local Reactogenicity Events During the 14 Days Post-vaccination</title>
          <description>Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination</title>
        <description>Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
        <time_frame>14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ccIIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
          </group>
          <group group_id="O2">
            <title>IIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination</title>
          <description>Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.</description>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Unsolicited and Severe Adverse Events</title>
        <description>The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.</description>
        <time_frame>42 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ccIIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
          </group>
          <group group_id="O2">
            <title>IIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
          </group>
        </group_list>
        <measure>
          <title>Unsolicited and Severe Adverse Events</title>
          <description>The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.</description>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>wheezing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>hand foot and mouth virus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Asthma Exacerbations Requiring Steroids</title>
        <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..</description>
        <time_frame>42 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ccIIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
          </group>
          <group group_id="O2">
            <title>IIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Asthma Exacerbations Requiring Steroids</title>
          <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..</description>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number Participants With Asthma Exacerbations Requiring Medical Attention</title>
        <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)</description>
        <time_frame>42 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ccIIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
          </group>
          <group group_id="O2">
            <title>IIV4</title>
            <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
          </group>
        </group_list>
        <measure>
          <title>Number Participants With Asthma Exacerbations Requiring Medical Attention</title>
          <description>For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>42 days from vaccination</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ccIIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
ccIIV4</description>
        </group>
        <group group_id="E2">
          <title>IIV4</title>
          <description>0.5 mL intramuscular injection&#xD;
IIV4</description>
        </group>
      </group_list>
      <serious_events>
        <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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hand foot and mouth disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </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="19" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Stomache Ache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Muscles Aches</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Decrease Appetite</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Local Reaction to Vaccine</sub_title>
                <description>includes mild, moderate and severe local reactions</description>
                <counts group_id="E1" events="19" subjects_affected="19" subjects_at_risk="20"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Feverish</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma Exacerbations</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </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>
    <point_of_contact>
      <name_or_title>Kathryn M. Edwards MD</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>615-322-8792</phone>
      <email>kathryn.edwards@vanderbilt.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/NCT02967393
org study id: IIV4/LAIV4/CDC
nct id: NCT02967393
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
This study is designed to note whether a larger safety study using quadrivalent live
      attenuated influenza vaccine (LAIV4) versus quadrivalent inactivated influenza vaccine
      (IIV4)(FLUARIX®), would be feasible in children with persistent asthma. Half of the patients
      in this study will receive the FLUARIX® influenza vaccine, while the other half will receive
      a cell cultured quadrivalent inactivated influenza vaccine (ccIIV4)(Flucelvax®) being used as
      a surrogate for LAIV4.
The association of an increased risk in wheezing following receipt of a live-attenuated
      influenza vaccine in children at least 2 years of age with a prior history of asthma or
      wheeze remains unclear.

      The Centers for Disease Control (CDC) and Prevention's Clinical Immunization Safety
      Assessment (CISA) planned to address a data safety gap regarding use of LAIV4 vaccine in
      children with asthma by conducting a 3-site randomized, non-inferiority prospective study.
      The main goal was to compare the safety of LAIV4 versus IIV4 in children 5-11 years with
      persistent asthma during the 2016-2017 influenza season. CDC and the CISA study sites
      developed a protocol and associated materials, and were poised to begin enrollment early
      during the 2016-2017 influenza season. However, after the June 22, 2016 Advisory Committee on
      Immunization Practices (ACIP) vote recommending against use of LAIV4 during the 2016-2017
      influenza season, CDC and study investigators decided to defer implementing a study using
      LAIV4 during the 2016-2017 influenza season. Investigators will reconsider initiating this
      study during the 2017-2018 influenza season if ACIP votes to reinstate LAIV4 use or new data
      become available; ACIP makes recommendations annually.

      The planned LAIV4 study had unique features in its design that previously had not been
      implemented in vaccine safety studies, including: 1) enrolling a substantial proportion of
      children with moderate-severe asthma 2) using digital peak flow meters and 3) collecting
      clinical data through multiple, complementary, measures for 42 days after vaccination. To
      capitalize on progress made during development of the study protocol and associated documents
      and procedures, CISA is proposing to carry out a study at the three sites to assess the
      feasibility of recruiting, enrolling, retaining, and collecting clinical data on children
      5-11 years with persistent asthma of varied levels of severity in an influenza vaccine safety
      study. Findings from this proposed feasibility study will facilitate improving the LAIV4
      study in the future if it goes forward through the CISA Project or in another venue. In
      2016-2017 season, FDA approved a new influenza vaccine for use in persons aged 4 years and
      older, Flucelvax® Quadrivalent (ccIIV4); ACIP incorporated this vaccine into its
      recommendations for the 2016-2017 influenza season. Therefore ccIIV4 will be used in place of
      LAIV4 for this feasibility study. There is no evidence that Flucelvax® increases the risk of
      wheezing in asthmatic children. The feasibility study also offers an opportunity to gain some
      additional descriptive safety data for this new vaccine in asthmatic children.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1.
time frame: 15 days
description: Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.
measure: Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data
time frame: Day 16 to 43
description: Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.
measure: Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements
time frame: 15 days
description: Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.
measure: Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42
time frame: Day 42
description: Parent will perform and document the digital peak flow for Day 42
measure: Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings
time frame: 15 days
description: Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.
measure: Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data
time frame: Day 3 to 6
description: Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data
measure: Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data.
time frame: Day 8-10
description: Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.
measure: Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data
time frame: Day 14 to 17
description: Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data
measure: Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data.
time frame: Day 29-31
description: Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.
measure: Feasibility Benchmark: Number of Parents That Respond to Day 44 Call
time frame: Day 44-47
description: Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.
measure: Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey
time frame: 42 days
description: Parent of each participant will be asked to complete a at the end of the study
measure: Severe Local Reactogenicity Events During the 14 Days Post-vaccination
time frame: 14 days
description: Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.
measure: Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination
time frame: 14 days
description: Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.
measure: Unsolicited and Severe Adverse Events
time frame: 42 days
description: The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.
measure: Number of Asthma Exacerbations Requiring Steroids
time frame: 42 days
description: For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..
measure: Number Participants With Asthma Exacerbations Requiring Medical Attention
time frame: 42 days
description: For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)
arm group label: IIV4
arm group type: Active Comparator
description: 0.5 mL intramuscular injection
arm group label: cc IIV4
arm group type: Active Comparator
description: 0.5 mL intramuscular injection
intervention type: Drug
intervention name: ccIIV4
arm group label: cc IIV4
other name: Flucelvax
intervention type: Drug
intervention name: IIV4
arm group label: IIV4
other name: Fluarix
criteria: 
gender: All
minimum age: 5 Years
maximum age: 11 Years
healthy volunteers: No
last name: Kathryn M Edwards, MD
role: Principal Investigator
affiliation: Vanderbilt Vaccine Research Program
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Kathryn Edwards
investigator title: Sarah H. Sell and Cornelius Vanderbilt Professor of Pediatrics
mesh term: Influenza, Human
mesh term: Asthma
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 