<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/NCT04436133</url>
  </required_header>
  <id_info>
    <org_study_id>GXIRB2020-0036</org_study_id>
    <nct_id>NCT04436133</nct_id>
  </id_info>
  <brief_title>Immunogenicity AND Safety Study of the 11 Valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha)</brief_title>
  <official_title>A Randomized, Blind, and Positive Control Design to Evaluate the Immunization Efficacy of 11 Valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 18-26 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Vaccine and Serum Institute, China</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chengdu Institute of Biological Products Co.,Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Simoon Record Pharma Information Consulting Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangxi Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Kantorico Statistical Technology Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Vaccine and Serum Institute, China</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>
      A total of 480 Chinese women aged 18-26 years old were enrolle，experimental group and the&#xD;
      control group were randomly assigned in a ratio of 3:1. 360 Chinese women in the experimental&#xD;
      group and 120 in the control group. All subjects enrolled in the upper arm deltoid muscle&#xD;
      were injected with 3 doses of test vaccine or control vaccine according to the 0, 2, and 6&#xD;
      months immunization program.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Actual">March 1, 2022</completion_date>
  <primary_completion_date type="Actual">March 1, 2022</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Anti-HPV neutralizing antibodies GMT</measure>
    <time_frame>30 days after full immunization</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Anti-HPV neutralizing antibody positive conversion rate（after full immunization 30 days）</measure>
    <time_frame>30 days after full immunization</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Collect all SAEs</measure>
    <time_frame>through study completion, an average of 13 months</time_frame>
    <description>Vaccine-related and unrelated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Collect AEs incidence</measure>
    <time_frame>Within 30 minutes of injection</time_frame>
    <description>Vaccine-related and unrelated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Collect AEs incidence</measure>
    <time_frame>Within 30 days after inoculation</time_frame>
    <description>All AEs: incidence of AEs related to vaccines and unrelated&#xD;
The rate of Solicited for AE&#xD;
Non-collective AEs: incidence of AEs related to vaccines and unrelated&#xD;
AE level 3 and above: incidence of vaccine-related and unrelated AEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>collect AEs leading subject to withdrawal</measure>
    <time_frame>through study completion, an average of 13months</time_frame>
    <description>Incidence of vaccine-related and unrelated AEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>collect All pregnancy conditions and pregnancy outcomes</measure>
    <time_frame>through study completion, an average of 13 months</time_frame>
    <description>collect pregnant woman Anti-HPV neutralizing antibody positive conversion rate and Anti-HPV neutralizing antibodies GMT</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">480</enrollment>
  <condition>HPV Infection</condition>
  <condition>HPV-Related Cervical Carcinoma</condition>
  <arm_group>
    <arm_group_label>vaccine group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Positive control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Biological/Vaccine: 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)</intervention_name>
    <description>Inject vaccine produced by ChinaVaccineSerum, containing HPV antigen protein, 270μg/1ml per bottle</description>
    <arm_group_label>vaccine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>9-valent HPV vaccine（Gardasil 9）</intervention_name>
    <description>Inject Gardasil 9 , containing HPV antigen protein, 270μg/0.5ml per bottle</description>
    <arm_group_label>Positive control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Chinese women aged 18-26 who can provide legal identification;&#xD;
&#xD;
          2. The subject has the ability to understand the research procedure and sign an informed&#xD;
             consent;&#xD;
&#xD;
          3. Subjects have the ability to read, understand, fill out diary cards/contact cards and&#xD;
             other research application forms and promise to participate in regular follow-up as&#xD;
             required by the research;&#xD;
&#xD;
          4. No previous history of HPV vaccination, no participation in HPV vaccine clinical&#xD;
             trials, and no plans to receive HPV vaccine during the study period; The subject was&#xD;
             not breastfeeding or pregnant (negative urine pregnancy test), did not have a birth&#xD;
             plan within 7 months of enrollment; and from day 1 of the last menstrual cycle to day&#xD;
             0 of the study, did not have sex with men or with men Effective contraception was used&#xD;
             during sex and no contraceptive failures occurred (examples of contraceptive failure&#xD;
             include male condom rupture during sex). And agreed to continue to take effective&#xD;
             contraceptive measures within the first 7 months after participating in the study&#xD;
             (effective contraceptive measures include: oral contraceptives, hormone patches,&#xD;
             intrauterine devices, condoms, cervical caps, etc.).&#xD;
&#xD;
        First dose exclusion criteria:&#xD;
&#xD;
          1. Previous history of cervical lesions (such as abnormal cervical cancer screening,&#xD;
             history of CIN disease) or history of hysterectomy surgery (vaginal or total&#xD;
             hysterectomy) or history of pelvic radiation therapy; previous history of external&#xD;
             genital diseases (such as vulvar epithelium) Neoplasia, intraepithelial neoplasia and&#xD;
             genital warts, etc.);&#xD;
&#xD;
          2. Previous history of severe allergic reactions requiring medical intervention for any&#xD;
             vaccine or drug (including yeast) (eg: anaphylactic shock, allergic throat edema,&#xD;
             allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus&#xD;
             reaction) Wait);&#xD;
&#xD;
          3. Immune function is impaired or has been diagnosed with congenital or acquired&#xD;
             immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia,&#xD;
             systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile Rheumatoid&#xD;
             arthritis (JRA), inflammatory bowel disease or other autoimmune diseases;&#xD;
&#xD;
          4. Long-term treatment with immunosuppressive agents, such as: long-term (more than 2&#xD;
             weeks in a row) treatment with glucocorticoids (eg, prednisone or similar drugs);&#xD;
&#xD;
          5. Receive any immunoglobulin or blood products within 3 months before vaccination, or&#xD;
             plan to receive such products before the 7th month of the study;&#xD;
&#xD;
          6. Received inactivated vaccine or recombinant vaccine within 14 days before vaccination,&#xD;
             or received any live vaccine within 28 days;&#xD;
&#xD;
          7. Loss of spleen or functional spleen, and removal of spleen or spleen caused by any&#xD;
             situation;&#xD;
&#xD;
          8. Has been diagnosed with a disease that may interfere with the progress or completion&#xD;
             of the study, such as: suffering from severe cardiovascular disease (pulmonary heart&#xD;
             disease, pulmonary edema), severe liver and kidney disease, diabetes with&#xD;
             complications, etc.; or has been diagnosed with Infectious diseases, such as: active&#xD;
             tuberculosis, hepatitis B, hepatitis C, etc.;&#xD;
&#xD;
          9. A history of convulsions, epilepsy, encephalopathy, mental illness, family history of&#xD;
             mental illness, etc.;&#xD;
&#xD;
         10. There are thrombocytopenia or other coagulation disorders that can be&#xD;
             contraindications to intramuscular injection; 11.3 days before the vaccination,&#xD;
             suffering from acute disease or in the acute onset of chronic disease or using&#xD;
             antipyretic, analgesic and anti-allergic drugs (such as: acetaminophen, ibuprofen,&#xD;
             aspirin, loratadine, cetaxidine Tirizine, etc.);&#xD;
&#xD;
        12.Body temperature before inoculation≥37.3℃(armpit body temperature); 13. People who have&#xD;
        a systolic blood pressure ≥140mmHg and/or a diastolic blood pressure ≥90mmHg before&#xD;
        enrollment; 14. Participate or plan to participate in other clinical trials (drugs,&#xD;
        vaccines and medical devices) during the study; 15. Plan to move out of the local area&#xD;
        before the end of the study or leave the area for a long time during the scheduled study&#xD;
        visit;&#xD;
&#xD;
        Exclusion criteria for second and third doses of vaccination:&#xD;
&#xD;
          1. Before vaccination (the day of vaccination), pregnant or urine pregnancy test (HCG) is&#xD;
             positive; Note: If the subject chooses to terminate the pregnancy, at least 6 weeks&#xD;
             after the end of pregnancy and the urine pregnancy test is negative on the day before&#xD;
             the vaccination, or the medical certificate of termination of pregnancy issued after&#xD;
             the end of pregnancy indicates that HCG levels have returned to normal levels, you can&#xD;
             continue Vaccination; if you choose to continue pregnancy, you will not be vaccinated&#xD;
             for subsequent doses.&#xD;
&#xD;
          2. Newly discovered or newly occurred conditions that meet the first dose exclusion&#xD;
             criteria (except Articles 1 and 13);&#xD;
&#xD;
          3. Other serious adverse events: The researcher decides whether to terminate the test&#xD;
             vaccination according to his treatment needs;&#xD;
&#xD;
          4. The investigator assessed any other reasons why the vaccination for the trial should&#xD;
             be terminated.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>26 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Liucheng Center for Disease Control and Prevention</name>
      <address>
        <city>Liuzhou</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Papillomavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04436133
org study id: GXIRB2020-0036
nct id: NCT04436133
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A total of 480 Chinese women aged 18-26 years old were enrolle，experimental group and the
      control group were randomly assigned in a ratio of 3:1. 360 Chinese women in the experimental
      group and 120 in the control group. All subjects enrolled in the upper arm deltoid muscle
      were injected with 3 doses of test vaccine or control vaccine according to the 0, 2, and 6
      months immunization program.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Anti-HPV neutralizing antibodies GMT
time frame: 30 days after full immunization
measure: Anti-HPV neutralizing antibody positive conversion rate（after full immunization 30 days）
time frame: 30 days after full immunization
measure: Collect all SAEs
time frame: through study completion, an average of 13 months
description: Vaccine-related and unrelated
measure: Collect AEs incidence
time frame: Within 30 minutes of injection
description: Vaccine-related and unrelated
measure: Collect AEs incidence
time frame: Within 30 days after inoculation
description: All AEs: incidence of AEs related to vaccines and unrelated
The rate of Solicited for AE
Non-collective AEs: incidence of AEs related to vaccines and unrelated
AE level 3 and above: incidence of vaccine-related and unrelated AEs
measure: collect AEs leading subject to withdrawal
time frame: through study completion, an average of 13months
description: Incidence of vaccine-related and unrelated AEs
measure: collect All pregnancy conditions and pregnancy outcomes
time frame: through study completion, an average of 13 months
description: collect pregnant woman Anti-HPV neutralizing antibody positive conversion rate and Anti-HPV neutralizing antibodies GMT
arm group label: vaccine group
arm group type: Experimental
arm group label: Positive control group
arm group type: Active Comparator
intervention type: Biological
intervention name: Biological/Vaccine: 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)
description: Inject vaccine produced by ChinaVaccineSerum, containing HPV antigen protein, 270μg/1ml per bottle
arm group label: vaccine group
intervention type: Biological
intervention name: 9-valent HPV vaccine（Gardasil 9）
description: Inject Gardasil 9 , containing HPV antigen protein, 270μg/0.5ml per bottle
arm group label: Positive control group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 26 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Papillomavirus Infections
mesh term: Vaccines
sharing ipd: No