<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/NCT03813940</url>
  </required_header>
  <id_info>
    <org_study_id>HPV-PRO-007</org_study_id>
    <nct_id>NCT03813940</nct_id>
  </id_info>
  <brief_title>Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)</brief_title>
  <official_title>An Open-Label, Single-Center Phase I Clinical Trial to Estimate Safety of the Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type) (E.Coli) in Healthy Adults Aged 18 to 45 Years</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>
  </sponsors>
  <source>Xiamen University</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>
      This phase I clinical study was designed to evaluate the safety of Recombinant Human&#xD;
      Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type)(E.Coli)(hereafter called HPV&#xD;
      vaccine), manufactured by Xiamen Innovax Biotech CO., LTD., in healthy adults aged 18-45&#xD;
      years old.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study would have 2 stages. In the first stage, around 12 healthy adults aged 18-45 (male&#xD;
      vs female,around 1:1)would receive 135μg/0.5ml of the HPV vaccine, the participants would be&#xD;
      actively followed up for 7 days, if no vaccine related serious adverse events(SAE) occurred&#xD;
      and the vaccine is well tolerated, another group of 12 healthy adults aged 18-45 (male vs&#xD;
      female,around 1:1)would be enrolled and would receive 270μg/0.5ml of the HPV vaccine. The&#xD;
      vaccine would be administered intramuscularly at day 0, month 1 and month 6. All the&#xD;
      participants would be actively monitored for adverse reactions/events for 1 month after each&#xD;
      injection. SAE during the trial were followed up. And blood, liver and kidney function&#xD;
      changes will be monitored before and 2 days after the first and third vaccination. Serum&#xD;
      samples from all the subjects would be collected on day 0 and month 7 to test immunogenicity&#xD;
      as exploratory analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">August 18, 2019</primary_completion_date>
  <phase>Phase 1</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Solicited local adverse reactions</measure>
    <time_frame>During the 7-day (Day 0-6) period following each vaccination</time_frame>
    <description>Solicited local adverse reactions occurred within 7 days after each vaccination;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Solicited systematic adverse reactions</measure>
    <time_frame>During the 7-day (Day 0-6) period following each vaccination</time_frame>
    <description>Solicited systematic adverse reactions occurred within 7 days after each vaccination;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Unsolicited adverse events</measure>
    <time_frame>Within 30 days (Day 0-29) after any vaccination</time_frame>
    <description>Unsolicited adverse reactions occurred within 30 days after each vaccination;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>throughout the study period, an average of 7 months</time_frame>
    <description>Serious adverse events occurred throughout the study;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinically Relevant Abnormalities in Blood Biochemistry</measure>
    <time_frame>Before and the second day after the first and third vaccination</time_frame>
    <description>Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase basophils, total bilirubin, direct bilirubin, indirect bilirubin, creatinine, urea nitrogen.&#xD;
Abnormalities reported include values outside the normal ranges: values higher than normal are designated as &quot;Above&quot; and values lower than normal as &quot;Below&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically Relevant Abnormalities in Hematological Parameters</measure>
    <time_frame>Before and the second day after the first and third vaccination</time_frame>
    <description>Hematological Parameters assessed in blood samples include platelets, red blood cell, hemoglobin and white blood cells.&#xD;
Abnormalities reported include values outside the normal ranges: values higher than normal are designated as &quot;Above&quot; and values lower than normal as &quot;Below&quot;.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific neutralizing antibody)</measure>
    <time_frame>month 7</time_frame>
    <description>To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific neutralizing antibody level on day 0 (before the 1st dose) and one month after dose 3</description>
  </other_outcome>
  <other_outcome>
    <measure>Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific IgG antibody)</measure>
    <time_frame>month 7</time_frame>
    <description>To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific IgG antibody level on day 0 (before the 1st dose) and one month after dose 3</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Condylomata Acuminata</condition>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>HPV Vaccine,135μg/0.5ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm would receive 135μg/0.5ml HPV vaccines</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HPV Vaccine,270μg/1.0ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm would receive 270μg/1.0ml HPV vaccines.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HPV Vaccine,135μg/0.5ml</intervention_name>
    <description>HPV vaccine (135μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule</description>
    <arm_group_label>HPV Vaccine,135μg/0.5ml</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HPV Vaccine,270μg/1.0ml</intervention_name>
    <description>HPV vaccine (270μg/1.0ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule</description>
    <arm_group_label>HPV Vaccine,270μg/1.0ml</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Health people aged between 18 and 45 years.&#xD;
&#xD;
          2. Judged as healthy and eligible for vaccination by the investigators through a&#xD;
             self-reported medical history and some physical examinations.&#xD;
&#xD;
          3. Able to comply with the requests of the study.&#xD;
&#xD;
          4. Written informed consent obtained from the participants.&#xD;
&#xD;
          5. Axillary temperature not higher than 37.0°C&#xD;
&#xD;
          6. Men, or non-pregnant women verified by a urine pregnancy test.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Pregnant or breastfeeding or plan to be pregnant within 7 months.&#xD;
&#xD;
          2. Use of any investigational product or non-registered product (drug or vaccine) within&#xD;
             30 days preceding the first dose of the study vaccine or plan to use during the study&#xD;
             period.&#xD;
&#xD;
          3. Received immunosuppressed, immunoregulation therapy or corticosteroid systemic therapy&#xD;
             for more than 14 days in the 6 months before entry, except local treatment.&#xD;
&#xD;
          4. Administration of any immunoglobulin or blood products within 3 months preceding the&#xD;
             first dose of the study vaccine or plan to use within 7 months.&#xD;
&#xD;
          5. Administration of any attenuated live vaccines within 21 days preceding the first dose&#xD;
             of the study vaccine or any subunit or inactivated vaccines within 14 days before&#xD;
             vaccination.&#xD;
&#xD;
          6. Had a fever (axillary temperature over 38°C) within 3 days or acute illness requiring&#xD;
             systemic antibiotics or antiviral treatment within 5 days before vaccination.&#xD;
&#xD;
          7. Having the plan to participate another clinical trial during the study period.&#xD;
&#xD;
          8. Received another HPV vaccine.&#xD;
&#xD;
          9. Immunodeficiency , primary disease of important organs, malignant tumor, or any immune&#xD;
             disease (such as systemic lupus erythematosus, arthritis pauperum, splenectomy or&#xD;
             functional asplenia or other disease which might affect immune response).&#xD;
&#xD;
         10. History of allergic disease or history of serious adverse events occurring after&#xD;
             vaccination, i.e., allergy, urticaria, dyspnea, angioneurotic edema or abdominal pain.&#xD;
&#xD;
         11. Asthma that required emergent treatment, hospitalization, oral or intravenous&#xD;
             corticosteroid for unstable condition within the past 2 years.&#xD;
&#xD;
         12. Having serious disease of internal medicine, such as hypertension(systolic blood&#xD;
             pressure &gt; 140mmHg or diastolic blood pressure &gt;90mmHg), cardiac disease, diabetes,&#xD;
             hyperthyroidism et al.&#xD;
&#xD;
         13. Diagnosed coagulant function abnormality or blood coagulation disorder. 14) The&#xD;
             results of blood routine test and blood biochemical test were abnormal. The grade was&#xD;
             2 or above.&#xD;
&#xD;
        15) Epilepsy, except fever epilepsy at under 2 years of age, alcohol-induced epilepsy in 3&#xD;
        years before abstinence, or idiopathic epilepsy requiring no treatment in the past 3 years.&#xD;
&#xD;
        16) Past or current two-stage affective psychosis, not well controlled in the past 2 years&#xD;
        or requiring drugs, or hve a tendency to commit suicide in the past 5 years.&#xD;
&#xD;
        17) Other medical, psychological, social or occupational factors that, according to the&#xD;
        investigators' judgment, might affect the individual's ability to obey the protocol or sign&#xD;
        the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Yue-Mei Hu, Bachelor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jiangsu Provincial Centre for Disease Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jiangsu Provincial Centre for Disease Control and Prevention</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>April 7, 2021</last_update_submitted>
  <last_update_submitted_qc>April 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2021</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 vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</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/NCT03813940
org study id: HPV-PRO-007
nct id: NCT03813940
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This phase I clinical study was designed to evaluate the safety of Recombinant Human
      Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type)(E.Coli)(hereafter called HPV
      vaccine), manufactured by Xiamen Innovax Biotech CO., LTD., in healthy adults aged 18-45
      years old.
The study would have 2 stages. In the first stage, around 12 healthy adults aged 18-45 (male
      vs female,around 1:1)would receive 135μg/0.5ml of the HPV vaccine, the participants would be
      actively followed up for 7 days, if no vaccine related serious adverse events(SAE) occurred
      and the vaccine is well tolerated, another group of 12 healthy adults aged 18-45 (male vs
      female,around 1:1)would be enrolled and would receive 270μg/0.5ml of the HPV vaccine. The
      vaccine would be administered intramuscularly at day 0, month 1 and month 6. All the
      participants would be actively monitored for adverse reactions/events for 1 month after each
      injection. SAE during the trial were followed up. And blood, liver and kidney function
      changes will be monitored before and 2 days after the first and third vaccination. Serum
      samples from all the subjects would be collected on day 0 and month 7 to test immunogenicity
      as exploratory analysis.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Solicited local adverse reactions
time frame: During the 7-day (Day 0-6) period following each vaccination
description: Solicited local adverse reactions occurred within 7 days after each vaccination;
measure: Solicited systematic adverse reactions
time frame: During the 7-day (Day 0-6) period following each vaccination
description: Solicited systematic adverse reactions occurred within 7 days after each vaccination;
measure: Unsolicited adverse events
time frame: Within 30 days (Day 0-29) after any vaccination
description: Unsolicited adverse reactions occurred within 30 days after each vaccination;
measure: Serious adverse events
time frame: throughout the study period, an average of 7 months
description: Serious adverse events occurred throughout the study;
measure: Clinically Relevant Abnormalities in Blood Biochemistry
time frame: Before and the second day after the first and third vaccination
description: Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase basophils, total bilirubin, direct bilirubin, indirect bilirubin, creatinine, urea nitrogen.
Abnormalities reported include values outside the normal ranges: values higher than normal are designated as "Above" and values lower than normal as "Below".
measure: Clinically Relevant Abnormalities in Hematological Parameters
time frame: Before and the second day after the first and third vaccination
description: Hematological Parameters assessed in blood samples include platelets, red blood cell, hemoglobin and white blood cells.
Abnormalities reported include values outside the normal ranges: values higher than normal are designated as "Above" and values lower than normal as "Below".
measure: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific neutralizing antibody)
time frame: month 7
description: To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific neutralizing antibody level on day 0 (before the 1st dose) and one month after dose 3
measure: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific IgG antibody)
time frame: month 7
description: To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific IgG antibody level on day 0 (before the 1st dose) and one month after dose 3
arm group label: HPV Vaccine,135μg/0.5ml
arm group type: Experimental
description: Participants in this arm would receive 135μg/0.5ml HPV vaccines
arm group label: HPV Vaccine,270μg/1.0ml
arm group type: Experimental
description: Participants in this arm would receive 270μg/1.0ml HPV vaccines.
intervention type: Biological
intervention name: HPV Vaccine,135μg/0.5ml
description: HPV vaccine (135μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule
arm group label: HPV Vaccine,135μg/0.5ml
intervention type: Biological
intervention name: HPV Vaccine,270μg/1.0ml
description: HPV vaccine (270μg/1.0ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule
arm group label: HPV Vaccine,270μg/1.0ml
criteria: 
gender: All
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: Yue-Mei Hu, Bachelor
role: Principal Investigator
affiliation: Jiangsu Provincial Centre for Disease Control and Prevention
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xiamen University
investigator full name: Jun Zhang
investigator title: Professor
mesh term: Uterine Cervical Neoplasms
mesh term: Vaccines