<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/NCT03753347</url>
  </required_header>
  <id_info>
    <org_study_id>H18-02607</org_study_id>
    <nct_id>NCT03753347</nct_id>
  </id_info>
  <brief_title>TITRE III: Influenza B Immunogenicity Investigation</brief_title>
  <official_title>TITRE III: TIV Infant/Toddler Response Evaluation - Influenza B Immunogenicity Investigation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British Columbia Centre for Disease Control</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vaccine Evaluation Center, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National en Santé Publique du Québec</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>British Columbia Centre for Disease Control</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Each winter, viruses belonging to two kinds of influenza A (&quot;A/H1N1&quot; &amp; &quot;A/H3N2&quot;) and two&#xD;
      kinds of influenza B (&quot;B/Yamagata&quot; &amp; &quot;B/Victoria&quot;) can cause illness. Historically, the&#xD;
      yearly influenza vaccine that was recommended in children was designed to protect against&#xD;
      both kinds of influenza A but only one kind of influenza B. In a series of trials conducted&#xD;
      between 2008-09 and 2010-11 (TITRE I, II, and IIB), the TITRE investigators measured antibody&#xD;
      response to influenza B in children who were primed with two doses of trivalent inactivated&#xD;
      influenza vaccine (TIV) containing B/Yamagata. Overall, the investigators found that 2 doses&#xD;
      of vaccine containing B/Yamagata did not adequately prime children for response to the&#xD;
      alternate B/Victoria antigen and that subsequent vaccine doses containing B/Victoria-lineage&#xD;
      antigen strongly boosted antibodies to the B/Yamagata antigen that was introduced during&#xD;
      first immunization priming, but with lower responses to B/Victoria.&#xD;
&#xD;
      For the first time since 2009-10, the recommended B/Victoria component of the seasonal&#xD;
      influenza vaccine has been changed, from B/Brisbane/60/2008 to B/Colorado/60/2007 for the&#xD;
      coming 2018-19 season. The investigators thus have a unique opportunity to clarify&#xD;
      lineage-specific influenza B responses in a well-characterized cohort of children originally&#xD;
      primed to Yamagata. The investigators' main interest is to assess whether TITRE I children&#xD;
      primed with two doses of B/Yamagata in 2008-09 have since or are now capable of achieving a&#xD;
      sufficient antibody response to B/Victoria following a single dose of 2018-19 QIV, ten years&#xD;
      after their initial TIV B/Yamagata priming exposure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Actual">April 12, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Seroprotection rate (SPR) for B/Victoria vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
    <description>SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroprotection rate (SPR) for B/Victoria vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
    <description>SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for B/Victoria vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for B/Victoria vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre ratio (GMTR) for B/Victoria vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion rate (SCR) for B/Victoria vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for B/Yamagata vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for B/Yamagata vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for B/Yamagata vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for B/Yamagata vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre ratio (GMTR) for B/Yamagata vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion rate (SCR) for B/Yamagata vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for A/H1N1 vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for A/H1N1 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for A/H1N1 vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for A/H1N1 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre ratio (GMTR) for A/H1N1 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion rate (SCR) for A/H1N1 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for A/H3N2 vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate (SPR) for A/H3N2 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for A/H3N2 vaccine strains</measure>
    <time_frame>Pre-vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre (GMT) for A/H3N2 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre ratio (GMTR) for A/H3N2 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion rate (SCR) for A/H3N2 vaccine strains</measure>
    <time_frame>4-6 weeks after receipt of QIV</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>influenza vaccine recipients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants of an earlier clinical trial (TITRE I) to receive one dose of the 2018-19 quadrivalent inactivated influenza vaccine</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>2018-19 quadrivalent inactivated influenza vaccine</intervention_name>
    <description>A single age-appropriate dose of 2018-19 quadrivalent inactivated influenza vaccine</description>
    <arm_group_label>influenza vaccine recipients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Child previously completed the TITRE I study in British Columbia or Quebec;&#xD;
&#xD;
          -  Child is healthy (stable chronic conditions acceptable) as established by health&#xD;
             assessment interview and verbal history-directed health examination;&#xD;
&#xD;
          -  Child is available and can complete all relevant procedures during the study period;&#xD;
&#xD;
          -  Parent or legal guardian is available and can be reached by phone during the study&#xD;
             period;&#xD;
&#xD;
          -  Parent/guardian provides written informed consent;&#xD;
&#xD;
          -  Parent/guardian is fluent in English/French&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Child has already received the 2018-19 seasonal (TIV or QIV) influenza vaccine;&#xD;
&#xD;
          -  Child has a bleeding condition that would prevent vaccine injection or blood&#xD;
             collection;&#xD;
&#xD;
          -  Child has known or suspected immunodeficiency;&#xD;
&#xD;
          -  Child has a suspected or known anaphylactic reaction to any of the vaccine components&#xD;
             used in this study;&#xD;
&#xD;
          -  Child has a health condition which, in the opinion of the investigator, would&#xD;
             interfere with the evaluation or pose a health risk to the child;&#xD;
&#xD;
          -  Child has received immune globulin or other blood products within the prior six weeks;&#xD;
&#xD;
          -  Child has received injected or oral steroids within the prior six weeks defined by&#xD;
             more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral&#xD;
             prednisolone &gt;0.5mL/kg/day or intravenous glucocorticoid steroid). Nasal, topical or&#xD;
             inhaled steroids are allowed;&#xD;
&#xD;
          -  Child has received any live vaccine within 28 days of the study vaccine or is&#xD;
             scheduled to receive live vaccine during the study period;&#xD;
&#xD;
          -  Child has received any inactivated vaccine within 14 days of the study vaccine;&#xD;
&#xD;
          -  Child is or will be enrolled in any other clinical trial of a drug, vaccine or medical&#xD;
             device during the study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>13 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Danuta M Skowronski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BC Centre for Disease Control</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>British Columbia Centre for Disease Control</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia (BC)</state>
        <zip>V5Z 4R4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <results_reference>
    <citation>Skowronski DM, Hottes TS, De Serres G, Ward BJ, Janjua NZ, Sabaiduc S, Chan T, Petric M. Influenza Beta/Victoria antigen induces strong recall of Beta/Yamagata but lower Beta/Victoria response in children primed with two doses of Beta/Yamagata. Pediatr Infect Dis J. 2011 Oct;30(10):833-9. doi: 10.1097/INF.0b013e31822db4dc.</citation>
    <PMID>21857263</PMID>
  </results_reference>
  <results_reference>
    <citation>Skowronski DM, Hottes TS, Chong M, De Serres G, Scheifele DW, Ward BJ, Halperin SA, Janjua NZ, Chan T, Sabaiduc S, Petric M. Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months. Pediatrics. 2011 Aug;128(2):e276-89. doi: 10.1542/peds.2010-2777. Epub 2011 Jul 18.</citation>
    <PMID>21768314</PMID>
  </results_reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>August 8, 2023</last_update_submitted>
  <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>British Columbia Centre for Disease Control</investigator_affiliation>
    <investigator_full_name>Danuta Skowronski</investigator_full_name>
    <investigator_title>Physician Epidemiologist, Influenza and Emerging Respiratory Pathogens</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03753347
org study id: H18-02607
nct id: NCT03753347
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Each winter, viruses belonging to two kinds of influenza A ("A/H1N1" & "A/H3N2") and two
      kinds of influenza B ("B/Yamagata" & "B/Victoria") can cause illness. Historically, the
      yearly influenza vaccine that was recommended in children was designed to protect against
      both kinds of influenza A but only one kind of influenza B. In a series of trials conducted
      between 2008-09 and 2010-11 (TITRE I, II, and IIB), the TITRE investigators measured antibody
      response to influenza B in children who were primed with two doses of trivalent inactivated
      influenza vaccine (TIV) containing B/Yamagata. Overall, the investigators found that 2 doses
      of vaccine containing B/Yamagata did not adequately prime children for response to the
      alternate B/Victoria antigen and that subsequent vaccine doses containing B/Victoria-lineage
      antigen strongly boosted antibodies to the B/Yamagata antigen that was introduced during
      first immunization priming, but with lower responses to B/Victoria.

      For the first time since 2009-10, the recommended B/Victoria component of the seasonal
      influenza vaccine has been changed, from B/Brisbane/60/2008 to B/Colorado/60/2007 for the
      coming 2018-19 season. The investigators thus have a unique opportunity to clarify
      lineage-specific influenza B responses in a well-characterized cohort of children originally
      primed to Yamagata. The investigators' main interest is to assess whether TITRE I children
      primed with two doses of B/Yamagata in 2008-09 have since or are now capable of achieving a
      sufficient antibody response to B/Victoria following a single dose of 2018-19 QIV, ten years
      after their initial TIV B/Yamagata priming exposure.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Seroprotection rate (SPR) for B/Victoria vaccine strains
time frame: Pre-vaccination
description: SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains
measure: Seroprotection rate (SPR) for B/Victoria vaccine strains
time frame: 4-6 weeks after receipt of QIV
description: SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains
measure: Geometric mean titre (GMT) for B/Victoria vaccine strains
time frame: Pre-vaccination
measure: Geometric mean titre (GMT) for B/Victoria vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre ratio (GMTR) for B/Victoria vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroconversion rate (SCR) for B/Victoria vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroprotection rate (SPR) for B/Yamagata vaccine strains
time frame: Pre-vaccination
measure: Seroprotection rate (SPR) for B/Yamagata vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre (GMT) for B/Yamagata vaccine strains
time frame: Pre-vaccination
measure: Geometric mean titre (GMT) for B/Yamagata vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre ratio (GMTR) for B/Yamagata vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroconversion rate (SCR) for B/Yamagata vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroprotection rate (SPR) for A/H1N1 vaccine strains
time frame: Pre-vaccination
measure: Seroprotection rate (SPR) for A/H1N1 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre (GMT) for A/H1N1 vaccine strains
time frame: Pre-vaccination
measure: Geometric mean titre (GMT) for A/H1N1 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre ratio (GMTR) for A/H1N1 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroconversion rate (SCR) for A/H1N1 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroprotection rate (SPR) for A/H3N2 vaccine strains
time frame: Pre-vaccination
measure: Seroprotection rate (SPR) for A/H3N2 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre (GMT) for A/H3N2 vaccine strains
time frame: Pre-vaccination
measure: Geometric mean titre (GMT) for A/H3N2 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Geometric mean titre ratio (GMTR) for A/H3N2 vaccine strains
time frame: 4-6 weeks after receipt of QIV
measure: Seroconversion rate (SCR) for A/H3N2 vaccine strains
time frame: 4-6 weeks after receipt of QIV
arm group label: influenza vaccine recipients
arm group type: Experimental
description: Participants of an earlier clinical trial (TITRE I) to receive one dose of the 2018-19 quadrivalent inactivated influenza vaccine
intervention type: Biological
intervention name: 2018-19 quadrivalent inactivated influenza vaccine
description: A single age-appropriate dose of 2018-19 quadrivalent inactivated influenza vaccine
arm group label: influenza vaccine recipients
criteria: 
gender: All
minimum age: 10 Years
maximum age: 13 Years
healthy volunteers: No
last name: Danuta M Skowronski, MD
role: Principal Investigator
affiliation: BC Centre for Disease Control
facility: 
country: Canada
citation: Skowronski DM, Hottes TS, De Serres G, Ward BJ, Janjua NZ, Sabaiduc S, Chan T, Petric M. Influenza Beta/Victoria antigen induces strong recall of Beta/Yamagata but lower Beta/Victoria response in children primed with two doses of Beta/Yamagata. Pediatr Infect Dis J. 2011 Oct;30(10):833-9. doi: 10.1097/INF.0b013e31822db4dc.
PMID: 21857263
citation: Skowronski DM, Hottes TS, Chong M, De Serres G, Scheifele DW, Ward BJ, Halperin SA, Janjua NZ, Chan T, Sabaiduc S, Petric M. Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months. Pediatrics. 2011 Aug;128(2):e276-89. doi: 10.1542/peds.2010-2777. Epub 2011 Jul 18.
PMID: 21768314
responsible party type: Principal Investigator
investigator affiliation: British Columbia Centre for Disease Control
investigator full name: Danuta Skowronski
investigator title: Physician Epidemiologist, Influenza and Emerging Respiratory Pathogens
mesh term: Influenza, Human