<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/NCT02263703</url>
  </required_header>
  <id_info>
    <org_study_id>2007/028</org_study_id>
    <nct_id>NCT02263703</nct_id>
  </id_info>
  <brief_title>Immunogenicity of HPV Vaccine in Immunosuppressed Children</brief_title>
  <official_title>Immunogenicity and Duration of Immunity in Immunosuppressed Children Vaccinated With Quadrivalent HPV Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of New South Wales</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sydney Children's Hospitals Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Women's and Children's Hospital, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of New South Wales</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Genital HPV is the necessary cause for cervical cancer, as well as a major contributing cause&#xD;
      of several other cancers and conditions. There are now effective vaccines against the main&#xD;
      oncogenic HPV types, HPV16 and 18.&#xD;
&#xD;
      Most research and discussion has focused on targeting the vaccine to young women and older&#xD;
      adolescents. Based on this, a national free HPV vaccination program for adolescent girls&#xD;
      commenced in 2007, in Australia. However, at the time of commencement, there had been no&#xD;
      research on the use of this vaccine in immunosuppressed. Therefore, information on the&#xD;
      immunogenicity, safety and duration of efficacy of HPV vaccine when administered to&#xD;
      immunosuppressed children is needed. This trial looked at a 3 dose schedule of quadrivalent&#xD;
      HPV vaccine in a range of immunosuppressed children, with the endpoint being immunogenicity,&#xD;
      followed for 5 years for duration of immunity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To determine the immunogenicity, safety and persistence of immunity following human&#xD;
      papillomavirus (HPV) vaccination in three groups of immunosuppressed children: recipients of&#xD;
      allogenic bone marrow transplant, recipients of renal and liver transplants, and patients&#xD;
      with juvenile chronic arthritis, inflammatory bowel disease and other autoimmune conditions&#xD;
      who are on longterm immunosuppressive therapy.&#xD;
&#xD;
      Significance: Immunosuppressed populations are diverse in terms of degree, type and duration&#xD;
      of immunosuppression. The study compares several groups in order to address the heterogeneity&#xD;
      of immunosuppression and how this affects vaccine response. BMT patients have extreme, severe&#xD;
      immunosuppression in the short term, but recover immune function with time. In contrast,&#xD;
      solid organ transplant recipients have ongoing, chronic immunosuppression. Although&#xD;
      successful cessation of immunosuppressives in liver transplant patients has been reported,&#xD;
      most patients require ongoing treatment. The inflammatory bowel disease group of patients&#xD;
      represents a non-transplant group who require ongoing, often low level immunosuppression,&#xD;
      often with corticosteroids. Our study will compare these three groups, followed up for five&#xD;
      years for duration of immunity. Time of vaccines, time of serological measures of immune&#xD;
      response are as follows.&#xD;
&#xD;
      Serum collections:&#xD;
&#xD;
      0 - Baseline (before HPV vaccine dose 1); 2 months - At the time of receipt of HPV vaccine&#xD;
      dose 2 (to measure response to dose 1); 6 months - At the time of receipt of HPV vaccine dose&#xD;
      3 (to measure response to dose 2); 7 months - 1 month after HPV vaccine dose 3; 12 months -&#xD;
      after HPV vaccine dose 1; 2 years after HPV vaccine dose 1; 3 years after HPV vaccine dose 1;&#xD;
      4 years after HPV vaccine dose 1; 5 years after HPV vaccine dose 1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2007</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>2 years</time_frame>
    <description>Indicator:&#xD;
Geometric mean four fold rises (with 95% confidence intervals) of the vaccine serotype specific IgG antibody in all participants.&#xD;
Proportion of subjects achieving a 4 fold rise in antibody titre for each serotype. Serum antibody levels will be measured using a Luminex immunoassay.&#xD;
Analysis: For each individual, the change in log-22FA levels for each serotype pre-post vaccination will be calculated. The average change will then be compared over time for each group and also between healthy and immunosuppressed groups using t-tests. Geometric mean titres of antibody for each serotype will be measured and compared at each follow up interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of immunity</measure>
    <time_frame>5 years</time_frame>
    <description>Interpretation of Results: Persistance of immunity will be measured over 5 years, as well as the comparison of immunogenicity by immune status.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Autoimmune Disease</condition>
  <condition>Juvenile Idiopathic Arthritis</condition>
  <condition>Inflammatory Bowel Disease</condition>
  <condition>Evidence of Liver Transplantation</condition>
  <condition>Kidney Transplant Infection</condition>
  <condition>Bone Marrow Transplant Infection</condition>
  <arm_group>
    <arm_group_label>HPV vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Quadrivalent HPV vaccine</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Quadrivalent HPV vaccine</intervention_name>
    <description>Three 0.5 mL doses will be given at time 0, 2 months after the 1st dose and then 6 months after the initial dose. For kidney transplant recipients the first dose will be at least 6 months post-transplant.</description>
    <arm_group_label>HPV vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Immunosuppressed patients with following diseases; Bone marrow transplant recipients,&#xD;
        liver transplant patients, renal transplant, Children with inflammatory bowel disease,&#xD;
        juvenile Idiopathic arthritis and autoimmune conditions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A platelet count of &lt;50&#xD;
&#xD;
          -  Immunoglobulin therapy within 3 months.&#xD;
&#xD;
          -  Yeast allergy&#xD;
&#xD;
          -  Any other known allergies to one of the vaccine component&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raina MacIntyre</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of New South Wales</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Public Health and Community Medicine</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <results_reference>
    <citation>MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine. 2016 Aug 5;34(36):4343-50. doi: 10.1016/j.vaccine.2016.06.049. Epub 2016 Jul 9.</citation>
    <PMID>27406936</PMID>
  </results_reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of New South Wales</investigator_affiliation>
    <investigator_full_name>Prof Raina MacIntyre</investigator_full_name>
    <investigator_title>Head of School and Professor of Infectious Diseases Epidemiology</investigator_title>
  </responsible_party>
  <keyword>HPV vaccine, children, immunocompromised</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Arthritis, Juvenile</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We would like to share publication(s) that may arise from the study when applicable.</ipd_description>
  </patient_data>
  <!-- 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/NCT02263703
org study id: 2007/028
nct id: NCT02263703
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Genital HPV is the necessary cause for cervical cancer, as well as a major contributing cause
      of several other cancers and conditions. There are now effective vaccines against the main
      oncogenic HPV types, HPV16 and 18.

      Most research and discussion has focused on targeting the vaccine to young women and older
      adolescents. Based on this, a national free HPV vaccination program for adolescent girls
      commenced in 2007, in Australia. However, at the time of commencement, there had been no
      research on the use of this vaccine in immunosuppressed. Therefore, information on the
      immunogenicity, safety and duration of efficacy of HPV vaccine when administered to
      immunosuppressed children is needed. This trial looked at a 3 dose schedule of quadrivalent
      HPV vaccine in a range of immunosuppressed children, with the endpoint being immunogenicity,
      followed for 5 years for duration of immunity.
To determine the immunogenicity, safety and persistence of immunity following human
      papillomavirus (HPV) vaccination in three groups of immunosuppressed children: recipients of
      allogenic bone marrow transplant, recipients of renal and liver transplants, and patients
      with juvenile chronic arthritis, inflammatory bowel disease and other autoimmune conditions
      who are on longterm immunosuppressive therapy.

      Significance: Immunosuppressed populations are diverse in terms of degree, type and duration
      of immunosuppression. The study compares several groups in order to address the heterogeneity
      of immunosuppression and how this affects vaccine response. BMT patients have extreme, severe
      immunosuppression in the short term, but recover immune function with time. In contrast,
      solid organ transplant recipients have ongoing, chronic immunosuppression. Although
      successful cessation of immunosuppressives in liver transplant patients has been reported,
      most patients require ongoing treatment. The inflammatory bowel disease group of patients
      represents a non-transplant group who require ongoing, often low level immunosuppression,
      often with corticosteroids. Our study will compare these three groups, followed up for five
      years for duration of immunity. Time of vaccines, time of serological measures of immune
      response are as follows.

      Serum collections:

      0 - Baseline (before HPV vaccine dose 1); 2 months - At the time of receipt of HPV vaccine
      dose 2 (to measure response to dose 1); 6 months - At the time of receipt of HPV vaccine dose
      3 (to measure response to dose 2); 7 months - 1 month after HPV vaccine dose 3; 12 months -
      after HPV vaccine dose 1; 2 years after HPV vaccine dose 1; 3 years after HPV vaccine dose 1;
      4 years after HPV vaccine dose 1; 5 years after HPV vaccine dose 1.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Immunogenicity
time frame: 2 years
description: Indicator:
Geometric mean four fold rises (with 95% confidence intervals) of the vaccine serotype specific IgG antibody in all participants.
Proportion of subjects achieving a 4 fold rise in antibody titre for each serotype. Serum antibody levels will be measured using a Luminex immunoassay.
Analysis: For each individual, the change in log-22FA levels for each serotype pre-post vaccination will be calculated. The average change will then be compared over time for each group and also between healthy and immunosuppressed groups using t-tests. Geometric mean titres of antibody for each serotype will be measured and compared at each follow up interval.
measure: Duration of immunity
time frame: 5 years
description: Interpretation of Results: Persistance of immunity will be measured over 5 years, as well as the comparison of immunogenicity by immune status.
arm group label: HPV vaccine
arm group type: Experimental
description: Quadrivalent HPV vaccine
intervention type: Biological
intervention name: Quadrivalent HPV vaccine
description: Three 0.5 mL doses will be given at time 0, 2 months after the 1st dose and then 6 months after the initial dose. For kidney transplant recipients the first dose will be at least 6 months post-transplant.
arm group label: HPV vaccine
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Raina MacIntyre
role: Principal Investigator
affiliation: The University of New South Wales
facility: 
country: Australia
citation: MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine. 2016 Aug 5;34(36):4343-50. doi: 10.1016/j.vaccine.2016.06.049. Epub 2016 Jul 9.
PMID: 27406936
responsible party type: Principal Investigator
investigator affiliation: The University of New South Wales
investigator full name: Prof Raina MacIntyre
investigator title: Head of School and Professor of Infectious Diseases Epidemiology
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Arthritis, Juvenile
mesh term: Inflammatory Bowel Diseases
mesh term: Autoimmune Diseases
sharing ipd: No
ipd description: We would like to share publication(s) that may arise from the study when applicable.