<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/NCT04425291</url>
  </required_header>
  <id_info>
    <org_study_id>4-HPV-3001</org_study_id>
    <nct_id>NCT04425291</nct_id>
  </id_info>
  <brief_title>Evaluate the Immunogenicity and Safety of 4-valent and 9-valent HPV Recombinant Vaccine in Chinese Healthy Females</brief_title>
  <official_title>A Randomized, Double-Blind and Positive-Controlled Phase 3 Study to Evaluate the Immunogenicity and Safety of the 4-valent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (Hansenula Polymorpha) and 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha) in Chinese Female Subjects Aged 20-45 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Bovax Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chongqing Bovax Biopharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Bovax Biotechnology Co., Ltd.</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 study will evaluate the immunogenicity and safety of 4-valent and 9-valent HPV&#xD;
      recombinant vaccine in Chinese healthy females 20 to 45 years of age.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Actual">September 6, 2021</completion_date>
  <primary_completion_date type="Actual">September 6, 2021</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of participants 20 to 45 Years of Age that achieve the neutralizing antibody serostatus cutoffs for seroconversion to HPV Types 6, 11, 16 and 18 at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The neutralizing antibody GMTs for HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants that achieve neutralizing antibody quadruple growth ratefor HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants that achieve neutralizing antibody quadruple growth rate or achieve the neutralizing antibody serostatus cutoffs for HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The neutralizing antibody GMTs for HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants that achieve neutralizing antibody quadruple growth ratefor HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants that achieve neutralizing antibody quadruple growth rate or achieve the neutralizing antibody serostatus cutoffs for HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.</measure>
    <time_frame>1 month post vaccination 3 (Month 7)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Report at Least 1 Solicited Injection-site and Systemic Adverse Event 30 minutes post any vaccination</measure>
    <time_frame>30 minutes post any vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Report at Least 1 Solicited Adverse Event 7 days post any vaccination</measure>
    <time_frame>7 days post any vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Report at Least 1 Solicited and Unsolicited Adverse Event 30 days post any vaccination</measure>
    <time_frame>30 days post any vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) from 1st vaccination to the completion of study</measure>
    <time_frame>Day 1 to 6 months post vaccination 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experience Pregnancy from 1st vaccination to the completion of study</measure>
    <time_frame>Day 1 to 6 months post vaccination 3</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1680</enrollment>
  <condition>Cervical Cancer</condition>
  <condition>Vulvar Cancer</condition>
  <condition>Vaginal Cancer</condition>
  <condition>CIN1</condition>
  <condition>CIN2</condition>
  <condition>CIN3</condition>
  <condition>VaIN1</condition>
  <condition>VaIN2</condition>
  <condition>VaIN3</condition>
  <condition>Genital Wart</condition>
  <condition>VIN 1</condition>
  <condition>VIN 2</condition>
  <condition>VIN 3</condition>
  <condition>AIS</condition>
  <arm_group>
    <arm_group_label>4-valent HPV Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm would receive 4-valent Human Papillomavirus (Types 6, 11, 16 and18) Recombinant Vaccine (Hansenula Polymorpha)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>9-valent HPV Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm would receive 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GARDASIL®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm would receive GARDASIL®</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4-valent HPV Vaccine</intervention_name>
    <description>Subjects received 3 doses of 4-valent HPV vaccine according to a 0, 2, 6-month schedule.</description>
    <arm_group_label>4-valent HPV Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>9-valent HPV Vaccine</intervention_name>
    <description>Subjects received 3 doses of 9-valent HPV vaccine according to a 0, 2, 6-month schedule.</description>
    <arm_group_label>9-valent HPV Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GARDASIL®</intervention_name>
    <description>Subjects received 3 doses of GARDASIL® according to a 0, 2, 6-month schedule.</description>
    <arm_group_label>GARDASIL®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Chinese women aged 20-45 who can provide legal identification;&#xD;
&#xD;
          2. The subject agreed to participate in the study, and voluntarily signs the informed&#xD;
             consent;&#xD;
&#xD;
          3. Subjects are able to understand the study procedures and participate in follow-up&#xD;
             according to the study requirements;&#xD;
&#xD;
          4. When the subjects were enrolled, the urine pregnancy test was negative, they were not&#xD;
             in the lactation period and had no family planning within 7 months after enrollment.2&#xD;
             weeks before included in the study, effective contraceptive measures has been adopted&#xD;
             and agreed to in the first seven months after the study (vaccinations after 1 months&#xD;
             ago) continue to adopt effective contraceptive measures (effective contraceptive&#xD;
             measures including the pill or condoms, etc );&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have been vaccinated with commercially available HPV vaccine in the past or planned to&#xD;
             be vaccinated with commercially available HPV vaccine during the study period;Or have&#xD;
             participated in a clinical trial of the HPV vaccine;&#xD;
&#xD;
          2. Has a history of cervical diseases, such as cervical screening showing abnormal&#xD;
             results including CIN or a history of hysterectomy (vaginal or total abdominal&#xD;
             hysterectomy) or pelvic radiation therapy. Has a history of genital diseases (such as&#xD;
             vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts,&#xD;
             vulvar cancer, vaginal cancer and anal cancer, etc.) or has a previous sexual history&#xD;
             (including syphilis, gonorrhea, chancre, venereal lymphatic granuloma, granuloma&#xD;
             inguinal);&#xD;
&#xD;
          3. A history of severe allergies requiring medical intervention, such as anaphylactic&#xD;
             shock, anaphylactic laryngeal edema, allergic purpura, thrombocytopenic purpura, local&#xD;
             allergic necrosis reaction (Arthus reaction), etc;&#xD;
&#xD;
          4. Have an acute illness or an acute episode of a chronic illness within 3 days prior to&#xD;
             vaccination or the use of antipyretic, analgesic and antiallergic drugs (e.g.,&#xD;
             acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.);&#xD;
&#xD;
          5. Subjects received inactivated or recombinant vaccines within 14 days prior to study&#xD;
             enrollment, or attenuated live vaccines within 28 days prior to study enrollment;&#xD;
&#xD;
          6. Subjects present with immune impairment or have been diagnosed with congenital or&#xD;
             acquired immune deficiency, HIV infection, lymphoma, leukemia, systemic lupus&#xD;
             erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA),&#xD;
             inflammatory bowel disease or other autoimmune diseases. Long-term immunosuppressive&#xD;
             therapy, e.g., long-term (more than 2 weeks) treatment with glucocorticoids (e.g.,&#xD;
             prednisone or similar drugs);&#xD;
&#xD;
          7. Has been diagnosed with a severe congenital malformation or chronic disease such as&#xD;
             Down syndrome, heart disease, liver disease, kidney disease, diabetes, etc., which may&#xD;
             interfere with the conduct or completion of the study;&#xD;
&#xD;
          8. Subject receives any immunoglobulin or blood product within 3 months prior to the&#xD;
             first dose of vaccination;&#xD;
&#xD;
          9. Participating in other (drug or vaccine) clinical trials prior to enrollment or&#xD;
             planning to participate during the study;&#xD;
&#xD;
         10. Has been diagnosed with an infectious disease, such as tuberculosis, viral hepatitis&#xD;
             and/or HIV infection;&#xD;
&#xD;
         11. A history or family history of convulsions, epilepsy, encephalopathy and mental&#xD;
             illness;&#xD;
&#xD;
         12. Have contraindications to intramuscular injection, such as having been diagnosed with&#xD;
             thrombocytopenia, any coagulation disorder or receiving anticoagulant therapy;&#xD;
&#xD;
         13. Absence of a spleen, functional absence of a spleen, and absence or removal of a&#xD;
             spleen in any case;&#xD;
&#xD;
         14. Body temperature ≥37.3℃ (underarm body temperature);&#xD;
&#xD;
         15. Subjects may be unable to comply with the study procedure, comply with the agreement,&#xD;
             or plan to permanently relocate from the region prior to completion of the study, or&#xD;
             may be permanently absent from the region during the scheduled visit;&#xD;
&#xD;
         16. In the opinion of the investigators, the subjects had any other factors that made them&#xD;
             unsuitable to participate in the clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Yangchun Center For Disease Prevention And Control</name>
      <address>
        <city>Yangchun</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 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>Condylomata Acuminata</mesh_term>
    <mesh_term>Vulvar Neoplasms</mesh_term>
    <mesh_term>Vaginal 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>
  <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/NCT04425291
org study id: 4-HPV-3001
nct id: NCT04425291
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study will evaluate the immunogenicity and safety of 4-valent and 9-valent HPV
      recombinant vaccine in Chinese healthy females 20 to 45 years of age.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Percentage of participants 20 to 45 Years of Age that achieve the neutralizing antibody serostatus cutoffs for seroconversion to HPV Types 6, 11, 16 and 18 at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: The neutralizing antibody GMTs for HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: Percentage of participants that achieve neutralizing antibody quadruple growth ratefor HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: Percentage of participants that achieve neutralizing antibody quadruple growth rate or achieve the neutralizing antibody serostatus cutoffs for HPV Types 6, 11, 16 and 18 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: The neutralizing antibody GMTs for HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: Percentage of participants that achieve neutralizing antibody quadruple growth ratefor HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: Percentage of participants that achieve neutralizing antibody quadruple growth rate or achieve the neutralizing antibody serostatus cutoffs for HPV Types 31, 33, 45 and 52 in participants 20 to 45 Years of Age at least 1 month post Dose 3.
time frame: 1 month post vaccination 3 (Month 7)
measure: Percentage of Participants Who Report at Least 1 Solicited Injection-site and Systemic Adverse Event 30 minutes post any vaccination
time frame: 30 minutes post any vaccination
measure: Percentage of Participants Who Report at Least 1 Solicited Adverse Event 7 days post any vaccination
time frame: 7 days post any vaccination
measure: Percentage of Participants Who Report at Least 1 Solicited and Unsolicited Adverse Event 30 days post any vaccination
time frame: 30 days post any vaccination
measure: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) from 1st vaccination to the completion of study
time frame: Day 1 to 6 months post vaccination 3
measure: Percentage of Participants Who Experience Pregnancy from 1st vaccination to the completion of study
time frame: Day 1 to 6 months post vaccination 3
arm group label: 4-valent HPV Vaccine
arm group type: Experimental
description: Participants in this arm would receive 4-valent Human Papillomavirus (Types 6, 11, 16 and18) Recombinant Vaccine (Hansenula Polymorpha)
arm group label: 9-valent HPV Vaccine
arm group type: Experimental
description: Participants in this arm would receive 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha)
arm group label: GARDASIL®
arm group type: Active Comparator
description: Participants in this arm would receive GARDASIL®
intervention type: Biological
intervention name: 4-valent HPV Vaccine
description: Subjects received 3 doses of 4-valent HPV vaccine according to a 0, 2, 6-month schedule.
arm group label: 4-valent HPV Vaccine
intervention type: Biological
intervention name: 9-valent HPV Vaccine
description: Subjects received 3 doses of 9-valent HPV vaccine according to a 0, 2, 6-month schedule.
arm group label: 9-valent HPV Vaccine
intervention type: Biological
intervention name: GARDASIL®
description: Subjects received 3 doses of GARDASIL® according to a 0, 2, 6-month schedule.
arm group label: GARDASIL®
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Condylomata Acuminata
mesh term: Vulvar Neoplasms
mesh term: Vaginal Neoplasms
mesh term: Vaccines
sharing ipd: No