A Phase III Clinical Trial of a 11-valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 9-45 Years

Overview

A total of 13500 Chinese women aged 18-45 years old were divided into three age groups: 18-26 years old, 27-35 years old, and 35-45 years old. The experimental group and the placebo group were randomly assigned in a ratio of 1:1. All subjects enrolled in the upper arm deltoid muscle were injected with 3 doses of test vaccine or placebo according to the 0, 2, and 6 months immunization program.

Eligibility

Inclusion Criteria:

• non-gynecological related
  1. *Chinese women with a history of sexual life who are 18-45 years old at the time of enrollment and can provide legal identification;
  2. *Axillary body temperature <37.3℃ on the day of enrollment;
  3. The subjects themselves have the ability to understand the clinical trial and voluntarily sign the informed consent;
  4. Subjects have the ability to read, understand, and fill out research application forms such as diary cards/contact cards, and promise to follow the research requirements participate in follow-up visits;
  5. No previous HPV vaccination history, no commercially available HPV vaccine during the study period (about 6 years after enrollment) plan of;
  6. The subject has a negative urine pregnancy test on the day before vaccination.
     • Gynecology related
  7. *Effective contraception was taken from day 1 of last menstrual cycle to day 0 of the

     study, and no childbearing within 7 months after enrollment plan.

  8. *Before the gynecological visit and within 48 hours before any subsequent visit that includes a gynecological sample collection: asexual life (including same-sex or opposite-sex anal, vaginal or genital contact), unwashed/washed vagina (Except for normal bathing outside the vagina）, no vaginal drugs or preparations are used.

Exclusion Criteria:

First dose exclusion criteria:

        (Visits may be rescheduled if the criteria described in the "*" option are met at
        screening)
        - Non-gynecological related
          1. * Those with abnormal blood pressure (systolic blood pressure ≥ 140mmHg and/or
             diastolic blood pressure ≥ 90mmHg) on physical examination before vaccination;
          2. *3 months prior to vaccination or planned to receive any immune globulin or blood
             products within 7 months of enrollment;
          3. *Received any vaccine within 14 days prior to vaccination, or received live vaccine
             within 28 days;
          4. *3 days before vaccination, suffering from acute febrile illness (body temperature
             ≥38.5℃) or using antipyretic, analgesic and antiallergic drugs (eg: acetaminophen,
             ibuprofen, aspirin, loratadine, cetirizine, etc.);
          5. History of severe allergies/conditions requiring medical intervention (e.g.
             Anaphylactic shock, anaphylactic laryngeal edema, anaphylactoid purpura,
             thrombocytopenic purpura, local allergic necrosis(Arthus reaction) etc.);
          6. Immunocompromised or diagnosed with congenital or acquired immunodeficiency, HIV
             infection, lymphoma, leukemia Blood disease, systemic lupus erythematosus (SLE),
             rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammation STD or other
             autoimmune disease;
          7. 1 month before vaccination or plan to receive immunosuppressive therapy within 7
             months after enrollment, such as oral administration for more than 2 consecutive weeks
             Oral or injectable systemic corticosteroid therapy (≥2 mg/kg/day or ≥20 mg/day
             prednisone or equivalent to prednisone) amount); however, topical medications (such as
             ointments, eye drops, inhalers, or nasal sprays) are not limited;
          8. Previous splenectomy or impaired spleen function;
          9. Those with previous or current severe liver, kidney and cardiovascular diseases,
             complicated diabetes, and malignant tumors;
         10. Have a history of epilepsy, convulsions, mental illness or a family history of mental
             illness;
         11. Suffering from thrombocytopenia or any coagulation disorder that can become a
             contraindication to intramuscular injection;
         12. Participate in other clinical studies (drugs, vaccines and medical devices) within 3
             months before vaccination or during the planned study period;
         13. The investigator believes that the subject has any other factors that are not suitable
             for participating in the clinical trial (such as: poor compliance or planning
             Permanent relocation from the area before the study is completed, etc.).
             - Gynecology related
         14. *Pregnant, breastfeeding, or within 6 weeks of pregnancy at the time of the first dose
             of the vaccine;
         15. *The subject is in the menstrual period;
         16. *Acute lower genital tract infection (such as acute vulvitis/vaginitis/cervicitis,
             etc.) found by the naked eye during gynecological examination;
         17. Previous history of abnormal cervical cancer screening or lesions (including HPV DNA
             positive, squamous intraepithelial lesion (SIL)or atypical squamous cells of
             undetermined significance (ASC-US), atypical squamous epithelial cells - excluding
             high-grade squamous cells Intraepithelial lesions (ASC-H), atypical glandular cells
             (AGC) or with cervical intraepithelial neoplasia (CIN),Adenocarcinoma in situ (AIS) or
             cervical cancer, etc.);
         18. Past or current anal and genital diseases (such as vulvar intraepithelial neoplasia,
             vaginal intraepithelial neoplasia, genital warts,vulvar cancer, vaginal cancer and
             anal cancer, etc.);
         19. Previous hysterectomy or pelvic radiation therapy or severe cervical/vaginal
             dysplasia.
        Exclusion criteria for 2nd and 3rd dose vaccination：
        If any of the following occurs, the investigator will terminate the subject's vaccination
        with the investigational vaccine.
          -  Meet the first dose exclusion criteria 5, 6, 7, 8, 9, 12;
          -  Any other reasons that, in the judgment of the investigator, warrant discontinuation
             of the investigational vaccination.