<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/NCT01735006</url>
  </required_header>
  <id_info>
    <org_study_id>HPV-PRO-003</org_study_id>
    <nct_id>NCT01735006</nct_id>
  </id_info>
  <brief_title>Efficacy and Immunogenicity Study of Recombinant Human Papillomavirus Bivalent（Type 16/18 ）Vaccine</brief_title>
  <official_title>A Phase III Multicenter, Randomized, Double-Blind, Placebo(Hepatitis E Vaccine)Controlled Study to Evaluate the Efficacy, Immunogenicity and Safety of a Recombinant(E.Coli)Human Papillomavirus Bivalent Vaccine in Healthy Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xiamen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xiamen Innovax Biotech Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministry of Science and Technology of the People´s Republic of China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Xiamen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase III clinical trial of the novel recombinant HPV 16/18 bivalent vaccine&#xD;
      manufactured by Xiamen Innovax Biotech CO., LTD. The primary objective of this study is to&#xD;
      demonstrate the efficacy of the vaccine against relevant outcomes in healthy women above 18&#xD;
      years old at enrolment. The secondary objectives are to evaluate the safety, immunogenicity&#xD;
      and immuno-persistence of the vaccine. Meanwhile, this study tries to compare the difference&#xD;
      of safety and immunogenicity among different lots. Approximately 6000 study subjects will be&#xD;
      enrolled and randomly stratified into 2 groups and receive human papillomavirus (HPV)&#xD;
      vaccine(three different lots) or commercialized hepatitis E vaccine(Hecolin) according to a&#xD;
      0-1-6 month schedule.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 22, 2012</start_date>
  <completion_date type="Actual">October 18, 2019</completion_date>
  <primary_completion_date type="Actual">August 1, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects With Histopathologically-confirmed CIN2+ and/or VIN2+ and/or VaIN2+ Associated With HPV-16 and/or -18 Cervical Infection</measure>
    <time_frame>expected 5-6 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Subjects With HPV-16 and/or -18 persistent cervical infection(6-month+ definition)</measure>
    <time_frame>expected 2-3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Reporting Solicited Local and General Symptoms</measure>
    <time_frame>Within 7 days after each vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Reporting Unsolicited Adverse Events</measure>
    <time_frame>Month 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Reporting Serious Adverse Events (SAEs)</measure>
    <time_frame>expected 5-6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of subjects with persistent cervical infection (12-month+ definition)associated with HPV-16 and/or HPV-18</measure>
    <time_frame>expected 5-6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of subjects Histopathologically-confirmed CIN1+ and/or VIN1+ and/or VaIN1+ associated with HPV-16 and/or -18 cervical infection</measure>
    <time_frame>expected 5-6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of subjects with incidence infection associated with HPV-16 and/or HPV-18</measure>
    <time_frame>expected 2-3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-HPV16 and anti-HPV18 seroconversion rates and geometric mean concentrations at Months 7</measure>
    <time_frame>month 7</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of subjects histopathologically confirmed CIN2+ and/or VIN2+ and/or VaIN2+ associated with oncogenic HPV types</measure>
    <time_frame>expected 5-6 years</time_frame>
    <description>Histopathologically confirmed CIN2+ and/or VIN2+ and/or VaIN2+ associated with oncogenic HPV types (e.g. HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) detected within the lesional component of the tissue specimen (by PCR).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7372</enrollment>
  <condition>Cervical Intraepithelial Neoplasia</condition>
  <condition>Cervical Cancer</condition>
  <condition>Vaginal Intraepithelial Neoplasia</condition>
  <condition>Vulvar Intraepithelial Neoplasia</condition>
  <condition>Persistent Infection</condition>
  <arm_group>
    <arm_group_label>HPV vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This dosage contains 40μg HPV 16 virus-like particle antigen and 20μg HPV 18 virus-like particle antigen adsorbed in alum-adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HEV vaccine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>commercialized HEV vaccine which contains 30μg HEV antigen adsorbed in alum-adjuvant</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HPV Vaccine</intervention_name>
    <description>3 doses at month 0,1 and 6</description>
    <arm_group_label>HPV vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HEV vaccine</intervention_name>
    <description>3 doses at month 0,1 and 6</description>
    <arm_group_label>HEV vaccine</arm_group_label>
    <other_name>Hecolin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female subjects between, and including, 18 and 45 years of age at the first&#xD;
             vaccination;&#xD;
&#xD;
          2. Healthy subjects as established by medical history and history-oriented clinical&#xD;
             examination;&#xD;
&#xD;
          3. Be able to understand and comply with the request of the protocol;&#xD;
&#xD;
          4. Without acute cervicitis;&#xD;
&#xD;
          5. Not pregnant;&#xD;
&#xD;
          6. Have intact cervix.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of any investigational or non-registered product (drug or vaccine)within 30 days&#xD;
             preceding the first vaccination, or plan to use during the study period;&#xD;
&#xD;
          2. Are using immunosuppressants;&#xD;
&#xD;
          3. Administration of immunoglobulin and/or any blood products within the three months&#xD;
             preceding the first vaccination or planned administration during the study period;&#xD;
&#xD;
          4. Vaccinated of inactivated vaccine 14 days or attenuated vaccine 21 days before the&#xD;
             enrollment;&#xD;
&#xD;
          5. Fever;&#xD;
&#xD;
          6. Concurrently participating another clinical trial;&#xD;
&#xD;
          7. Has received vaccines against HPV 16/18 ;&#xD;
&#xD;
          8. Immunodeficient;&#xD;
&#xD;
          9. History of allergic disease;&#xD;
&#xD;
         10. Serious medical disorders;&#xD;
&#xD;
         11. Blood coagulation disorders;&#xD;
&#xD;
         12. Epilepsy;&#xD;
&#xD;
         13. Unable to comply with protocol due to the mental illness;&#xD;
&#xD;
         14. Visible Condyloma;&#xD;
&#xD;
         15. Pregnant or breast-feeding women;&#xD;
&#xD;
         16. vergins;&#xD;
&#xD;
         17. Have more than 4 sexual partners.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Zhang, Master</last_name>
    <role>Study Chair</role>
    <affiliation>Xiamen University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Youlin Qiao, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ting Wu, Ph. D</last_name>
    <role>Study Director</role>
    <affiliation>Xiamen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Institute ＆ Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>November 18, 2012</study_first_submitted>
  <study_first_submitted_qc>November 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>February 21, 2020</last_update_submitted>
  <last_update_submitted_qc>February 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xiamen University</investigator_affiliation>
    <investigator_full_name>Jun Zhang</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>Human Papillomavirus 16</keyword>
  <keyword>Human Papillomavirus 18</keyword>
  <keyword>vaccine</keyword>
  <keyword>Cervical Intraepithelial Neoplasia</keyword>
  <keyword>cervical Cancer</keyword>
  <keyword>Vaginal intraepithelial neoplasia</keyword>
  <keyword>Vulvar intraepithelial neoplasia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Persistent Infection</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma in Situ</mesh_term>
    <mesh_term>Uterine Cervical Dysplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_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/NCT01735006
org study id: HPV-PRO-003
nct id: NCT01735006
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This is a Phase III clinical trial of the novel recombinant HPV 16/18 bivalent vaccine
      manufactured by Xiamen Innovax Biotech CO., LTD. The primary objective of this study is to
      demonstrate the efficacy of the vaccine against relevant outcomes in healthy women above 18
      years old at enrolment. The secondary objectives are to evaluate the safety, immunogenicity
      and immuno-persistence of the vaccine. Meanwhile, this study tries to compare the difference
      of safety and immunogenicity among different lots. Approximately 6000 study subjects will be
      enrolled and randomly stratified into 2 groups and receive human papillomavirus (HPV)
      vaccine(three different lots) or commercialized hepatitis E vaccine(Hecolin) according to a
      0-1-6 month schedule.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Subjects With Histopathologically-confirmed CIN2+ and/or VIN2+ and/or VaIN2+ Associated With HPV-16 and/or -18 Cervical Infection
time frame: expected 5-6 years
measure: Number of Subjects With HPV-16 and/or -18 persistent cervical infection(6-month+ definition)
time frame: expected 2-3 years
measure: Number of Subjects Reporting Solicited Local and General Symptoms
time frame: Within 7 days after each vaccination
measure: Number of Subjects Reporting Unsolicited Adverse Events
time frame: Month 7
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
time frame: expected 5-6 years
measure: number of subjects with persistent cervical infection (12-month+ definition)associated with HPV-16 and/or HPV-18
time frame: expected 5-6 years
measure: number of subjects Histopathologically-confirmed CIN1+ and/or VIN1+ and/or VaIN1+ associated with HPV-16 and/or -18 cervical infection
time frame: expected 5-6 years
measure: number of subjects with incidence infection associated with HPV-16 and/or HPV-18
time frame: expected 2-3 years
measure: Anti-HPV16 and anti-HPV18 seroconversion rates and geometric mean concentrations at Months 7
time frame: month 7
measure: Number of subjects histopathologically confirmed CIN2+ and/or VIN2+ and/or VaIN2+ associated with oncogenic HPV types
time frame: expected 5-6 years
description: Histopathologically confirmed CIN2+ and/or VIN2+ and/or VaIN2+ associated with oncogenic HPV types (e.g. HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) detected within the lesional component of the tissue specimen (by PCR).
arm group label: HPV vaccine
arm group type: Experimental
description: This dosage contains 40μg HPV 16 virus-like particle antigen and 20μg HPV 18 virus-like particle antigen adsorbed in alum-adjuvant
arm group label: HEV vaccine
arm group type: Placebo Comparator
description: commercialized HEV vaccine which contains 30μg HEV antigen adsorbed in alum-adjuvant
intervention type: Biological
intervention name: HPV Vaccine
description: 3 doses at month 0,1 and 6
arm group label: HPV vaccine
intervention type: Biological
intervention name: HEV vaccine
description: 3 doses at month 0,1 and 6
arm group label: HEV vaccine
other name: Hecolin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jun Zhang, Master
role: Study Chair
affiliation: Xiamen University
last name: Youlin Qiao, Ph.D
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Ting Wu, Ph. D
role: Study Director
affiliation: Xiamen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xiamen University
investigator full name: Jun Zhang
investigator title: professor
mesh term: Persistent Infection
mesh term: Uterine Cervical Neoplasms
mesh term: Neoplasms
mesh term: Carcinoma in Situ
mesh term: Uterine Cervical Dysplasia
mesh term: Vaccines