<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/NCT02968420</url>
  </required_header>
  <id_info>
    <org_study_id>H16-00700</org_study_id>
    <nct_id>NCT02968420</nct_id>
  </id_info>
  <brief_title>Long Term Immune Memory Responses to HPV Vaccination Following 2 vs 3 Doses of Quad-HPV Vaccine</brief_title>
  <acronym>Merck08</acronym>
  <official_title>Long Term Immune Memory Responses to Human Papillomavirus (HPV) Vaccination Following 2 Verses 3 Doses of Quadrivalent HPV Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Canada Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of British Columbia</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of this study is to further understand the memory response to HPV vaccination&#xD;
      in subjects who have received 2 versus 3 doses of quadrivalent HPV vaccine. Although memory&#xD;
      responses can be detected shortly after immunization, the best approach to measure the&#xD;
      long-lasting anamnestic response is to challenge with a booster dose years (&gt; 5) after the&#xD;
      original exposure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, interventional study to evaluate long term memory response to Q-HPV&#xD;
      vaccination and to natural infection. Memory response will be assessed by measuring&#xD;
      seroprotection 8-10 years post Q-HPV vaccination and to challenge with a booster dose years&#xD;
      after the original exposure to measure the long-lasting anamnestic response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Actual">May 15, 2019</completion_date>
  <primary_completion_date type="Actual">May 15, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>B Memory Cell Response (% of Memory B Cells That Are Antigen-specific)</measure>
    <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the B memory cell populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasmablast Response (% of All B Cells That Are Plasmablasts)</measure>
    <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the plasmablast populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences)</measure>
    <time_frame>At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Antibody Response (cLIA) - Geometric Mean Titer</measure>
    <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Antibody Response (cLIA) - Geometric Mean Titer</measure>
    <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Antibody Response (Total IgG) - Geometric Mean Titer</measure>
    <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Antibody Response (Total IgG) - Geometric Mean Titer</measure>
    <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
    <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Human Papillomavirus</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human Papillomavirus 9-valent Vaccine, Recombinant</intervention_name>
    <description>All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <other_name>Gardasil9</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent provided by the participant.&#xD;
&#xD;
          -  Participant whom the investigator believes can and will comply with the requirements&#xD;
             of the protocol.&#xD;
&#xD;
          -  General good health.&#xD;
&#xD;
          -  Immunized with Q-HPV vaccine between the ages of 9-13 or 16 to 26 years on the BCGov01&#xD;
             study or the BC provincial program.&#xD;
&#xD;
          -  Participant who is of child bearing potential must be willing to ensure that they or&#xD;
             their partner use effective contraception during the study. Examples of effective&#xD;
             methods of birth control include:&#xD;
&#xD;
               -  Abstinence (no sexual activity)&#xD;
&#xD;
               -  Hormonal contraceptives including oral, injectable, implants &amp; skin patches&#xD;
&#xD;
               -  Intrauterine device (IUD)&#xD;
&#xD;
               -  Male partner sterilization&#xD;
&#xD;
               -  Male condom combined with a vaginal spermicide (foam, gel, film, cream or&#xD;
                  suppository)&#xD;
&#xD;
               -  Male condom combined with a female diaphragm, whether with or without a vaginal&#xD;
                  spermicide (foam, gel, cream, or suppository)&#xD;
&#xD;
               -  Adequate contraception does not apply to participants with same sex partners,&#xD;
                  when this is their preferred and usual lifestyle&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received more than 3 doses of Q-HPV vaccine&#xD;
&#xD;
          -  Received any doses of HPV9 vaccine&#xD;
&#xD;
          -  Systemic hypersensitivity to Q-HPV vaccine or HPV9 vaccine or severe reaction to any&#xD;
             previous dose of Q-HPV vaccine.&#xD;
&#xD;
          -  Receipt of blood or blood product within 3 months prior to Visit 1.&#xD;
&#xD;
          -  Receipt of a live vaccine within 28 days or an inactive vaccine within 14 days of&#xD;
             Visit 1&#xD;
&#xD;
          -  Immune compromise resulting from disease or immunosuppressive systemic medication use&#xD;
             within 3 months prior to Visit 1.&#xD;
&#xD;
          -  Inadequate participant fluency in English to provide fully informed consent.&#xD;
&#xD;
          -  Participant who is currently pregnant or planning a pregnancy during the course of the&#xD;
             trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tobi Kollmann, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vaccine Evaluation Center, University of British Columbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Manish Sadarangani, BM BCh DPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vaccine Evaluation Center, University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vaccine Evaluation Center, BC Children's Hospital Research Institute</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.</citation>
    <PMID>17499406</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 19, 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 6, 2021</results_first_submitted>
  <results_first_submitted_qc>June 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 25, 2021</results_first_posted>
  <last_update_submitted>June 23, 2021</last_update_submitted>
  <last_update_submitted_qc>June 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Manish Sadarangani</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>If IPD is required, please contact the study team for further discussions- any sharing will be dependent on alignment with original informed consent obtained from study participants and in agreement with the study team.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT02968420/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT02968420/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group 1</title>
          <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="P2">
          <title>Group 2</title>
          <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="P3">
          <title>Group 3</title>
          <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1</title>
          <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="B2">
          <title>Group 2</title>
          <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="B3">
          <title>Group 3</title>
          <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="B4">
          <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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.05" spread=".89"/>
                    <measurement group_id="B2" value="21.95" spread="1.66"/>
                    <measurement group_id="B3" value="30.02" spread="3.34"/>
                    <measurement group_id="B4" value="24.67" spread="4.41"/>
                  </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="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chinese</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other/mixed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.60" spread="18.03"/>
                    <measurement group_id="B2" value="72.25" spread="26.51"/>
                    <measurement group_id="B3" value="73.75" spread="15.40"/>
                    <measurement group_id="B4" value="73.53" spread="19.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>Kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.37" spread="6.69"/>
                    <measurement group_id="B2" value="24.23" spread="6.15"/>
                    <measurement group_id="B3" value="25.63" spread="3.42"/>
                    <measurement group_id="B4" value="25.74" spread="5.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>B Memory Cell Response (% of Memory B Cells That Are Antigen-specific)</title>
        <description>To compare the B memory cell populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
        <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>B Memory Cell Response (% of Memory B Cells That Are Antigen-specific)</title>
          <description>To compare the B memory cell populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
          <units>% of memory B cells that are Ag-specific</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HPV16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.61" spread="0.49"/>
                    <measurement group_id="O2" value="0.94" spread="0.94"/>
                    <measurement group_id="O3" value="0.36" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" spread="0.18"/>
                    <measurement group_id="O2" value="0.11" spread="0.13"/>
                    <measurement group_id="O3" value="0.03" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Plasmablast Response (% of All B Cells That Are Plasmablasts)</title>
        <description>To compare the plasmablast populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
        <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasmablast Response (% of All B Cells That Are Plasmablasts)</title>
          <description>To compare the plasmablast populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months</description>
          <units>% of all B cells that are plasmablasts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.37" spread="2.51"/>
                    <measurement group_id="O2" value="3.14" spread="3.53"/>
                    <measurement group_id="O3" value="5.37" spread="6.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences)</title>
        <description>To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series</description>
        <time_frame>At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <population>The extent of somatic hypermutation was planned by comparing the nucleotide sequences of the heavy and light chain variable region sequences of each antibody cloned in this study to germ line sequences of these genes in public databases. This was not possible due to insufficient quality of DNA for sequencing.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences)</title>
          <description>To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series</description>
          <population>The extent of somatic hypermutation was planned by comparing the nucleotide sequences of the heavy and light chain variable region sequences of each antibody cloned in this study to germ line sequences of these genes in public databases. This was not possible due to insufficient quality of DNA for sequencing.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Antibody Response (cLIA) - Geometric Mean Titer</title>
        <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
        <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Antibody Response (cLIA) - Geometric Mean Titer</title>
          <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
          <units>antibody titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HPV6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="338" lower_limit="111" upper_limit="1027"/>
                    <measurement group_id="O2" value="1864" lower_limit="1411" upper_limit="2461"/>
                    <measurement group_id="O3" value="699" lower_limit="129" upper_limit="3780"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1277" lower_limit="592" upper_limit="2753"/>
                    <measurement group_id="O2" value="5071" lower_limit="2361" upper_limit="10892"/>
                    <measurement group_id="O3" value="3807" lower_limit="1096" upper_limit="13224"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4922" lower_limit="1765" upper_limit="13731"/>
                    <measurement group_id="O2" value="15237" lower_limit="6966" upper_limit="33328"/>
                    <measurement group_id="O3" value="10122" lower_limit="3475" upper_limit="29481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="855" lower_limit="461" upper_limit="1585"/>
                    <measurement group_id="O2" value="2140" lower_limit="897" upper_limit="5105"/>
                    <measurement group_id="O3" value="807" lower_limit="305" upper_limit="2134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Antibody Response (cLIA) - Geometric Mean Titer</title>
        <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
        <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Antibody Response (cLIA) - Geometric Mean Titer</title>
          <description>To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
          <units>antibody titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HPV6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1313" lower_limit="376" upper_limit="4586"/>
                    <measurement group_id="O2" value="2722" lower_limit="1472" upper_limit="5033"/>
                    <measurement group_id="O3" value="815" lower_limit="135" upper_limit="4924"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3430" lower_limit="1418" upper_limit="8299"/>
                    <measurement group_id="O2" value="6042" lower_limit="3255" upper_limit="11214"/>
                    <measurement group_id="O3" value="5778" lower_limit="2919" upper_limit="11439"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21135" lower_limit="11337" upper_limit="39399"/>
                    <measurement group_id="O2" value="21768" lower_limit="11797" upper_limit="40170"/>
                    <measurement group_id="O3" value="18930" lower_limit="11126" upper_limit="32208"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3326" lower_limit="1197" upper_limit="9245"/>
                    <measurement group_id="O2" value="2615" lower_limit="1033" upper_limit="6620"/>
                    <measurement group_id="O3" value="1312" lower_limit="676" upper_limit="2548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Antibody Response (Total IgG) - Geometric Mean Titer</title>
        <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
        <time_frame>At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Antibody Response (Total IgG) - Geometric Mean Titer</title>
          <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
          <units>antibody titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HPV6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1263" lower_limit="437" upper_limit="3650"/>
                    <measurement group_id="O2" value="6079" lower_limit="3682" upper_limit="10036"/>
                    <measurement group_id="O3" value="3712" lower_limit="1036" upper_limit="13302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1009" lower_limit="308" upper_limit="3306"/>
                    <measurement group_id="O2" value="5184" lower_limit="2644" upper_limit="10164"/>
                    <measurement group_id="O3" value="3371" lower_limit="947" upper_limit="11997"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4715" lower_limit="1358" upper_limit="16368"/>
                    <measurement group_id="O2" value="10962" lower_limit="3489" upper_limit="34438"/>
                    <measurement group_id="O3" value="7607" lower_limit="1379" upper_limit="41972"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1418" lower_limit="450" upper_limit="4473"/>
                    <measurement group_id="O2" value="3694" lower_limit="1522" upper_limit="8964"/>
                    <measurement group_id="O3" value="946" lower_limit="296" upper_limit="3026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Antibody Response (Total IgG) - Geometric Mean Titer</title>
        <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
        <time_frame>At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1</title>
            <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O2">
            <title>Group 2</title>
            <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
          <group group_id="O3">
            <title>Group 3</title>
            <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Antibody Response (Total IgG) - Geometric Mean Titer</title>
          <description>To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 &amp; 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose</description>
          <units>antibody titer</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HPV6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4579" lower_limit="1930" upper_limit="10865"/>
                    <measurement group_id="O2" value="7308" lower_limit="4781" upper_limit="11172"/>
                    <measurement group_id="O3" value="7371" lower_limit="3757" upper_limit="14460"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3234" lower_limit="1016" upper_limit="10297"/>
                    <measurement group_id="O2" value="6637" lower_limit="3810" upper_limit="11559"/>
                    <measurement group_id="O3" value="6271" lower_limit="3309" upper_limit="11884"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25808" lower_limit="10472" upper_limit="63603"/>
                    <measurement group_id="O2" value="32051" lower_limit="18808" upper_limit="54618"/>
                    <measurement group_id="O3" value="12364" lower_limit="2957" upper_limit="51689"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HPV18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6363" lower_limit="2371" upper_limit="17082"/>
                    <measurement group_id="O2" value="4985" lower_limit="1737" upper_limit="14304"/>
                    <measurement group_id="O3" value="1813" lower_limit="805" upper_limit="4082"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected at Day 7 (+/-1) and Day 30 (+/-3) following booster dose.</time_frame>
      <desc>Provincially reportable and serious adverse events only were collected.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group 1</title>
          <description>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="E2">
          <title>Group 2</title>
          <description>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
        <group group_id="E3">
          <title>Group 3</title>
          <description>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.&#xD;
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </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>Dr. Manish Sadarangani</name_or_title>
      <organization>Vaccine Evaluation Center</organization>
      <phone>604-875-2422</phone>
      <email>msadarangani@bcchr.ubc.ca</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/NCT02968420
org study id: H16-00700
nct id: NCT02968420
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overall aim of this study is to further understand the memory response to HPV vaccination
      in subjects who have received 2 versus 3 doses of quadrivalent HPV vaccine. Although memory
      responses can be detected shortly after immunization, the best approach to measure the
      long-lasting anamnestic response is to challenge with a booster dose years (> 5) after the
      original exposure.
This is a single center, interventional study to evaluate long term memory response to Q-HPV
      vaccination and to natural infection. Memory response will be assessed by measuring
      seroprotection 8-10 years post Q-HPV vaccination and to challenge with a booster dose years
      after the original exposure to measure the long-lasting anamnestic response.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: B Memory Cell Response (% of Memory B Cells That Are Antigen-specific)
time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the B memory cell populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months
measure: Plasmablast Response (% of All B Cells That Are Plasmablasts)
time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the plasmablast populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months
measure: Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences)
time frame: At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series
measure: Serum Antibody Response (cLIA) - Geometric Mean Titer
time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose
measure: Serum Antibody Response (cLIA) - Geometric Mean Titer
time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose
measure: Serum Antibody Response (Total IgG) - Geometric Mean Titer
time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose
measure: Serum Antibody Response (Total IgG) - Geometric Mean Titer
time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
description: To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose
arm group label: Group 1
arm group type: Active Comparator
description: Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.
arm group label: Group 2
arm group type: Active Comparator
description: Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.
arm group label: Group 3
arm group type: Active Comparator
description: Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study.
intervention type: Biological
intervention name: Human Papillomavirus 9-valent Vaccine, Recombinant
description: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
other name: Gardasil9
criteria: 
gender: Female
minimum age: 17 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tobi Kollmann, MD PhD
role: Principal Investigator
affiliation: Vaccine Evaluation Center, University of British Columbia
last name: Manish Sadarangani, BM BCh DPhil
role: Principal Investigator
affiliation: Vaccine Evaluation Center, University of British Columbia
facility: 
country: Canada
citation: Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.
PMID: 17499406
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Manish Sadarangani
investigator title: Principal Investigator
sharing ipd: No
ipd description: If IPD is required, please contact the study team for further discussions- any sharing will be dependent on alignment with original informed consent obtained from study participants and in agreement with the study team.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 