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

A Multicenter Randomized, Blinded, Placebo-controlled Phase III Clinical Trial Evaluating the Protective Efficacy, Safety and Immunogenicity of a 11-valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 9-45 Years

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.

Study Overview

• Status: Recruiting
• Conditions: HPV-Related Carcinoma; HPV InfectioN
• Intervention / Treatment: Biological: 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha); Biological: placebo

• Study Type: Interventional
• Enrollment (Estimated): 13500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhaojun Mo; Phone Number: （+86）15177771508; Email: mozhj@126.com

Study Locations

• China
  • Guangxi
    • Hechi, Guangxi, China, 546300
      • Not yet recruiting
      • Hechi Yizhou District Center for Disease Control and Prevention
      • Contact: ming han; Phone Number: （+86）18934923075
    • Hezhou, Guangxi, China, 542899
      • Not yet recruiting
      • Hezhou Center for Disease Control and Prevention
      • Contact: Jian biao Li; Phone Number: （+86）18978463935
  • Hunan
    • Lianyuan, Hunan, China, 417100
      • Recruiting
      • Lianyuan Center for Disease Control and Prevention
      • Contact: Hui Deng; Phone Number: （+86）13789255955
    • Wuxi, Hunan, China, 426100
      • Recruiting
      • Qiyang Center for Disease Control and Prevention
      • Contact: Ling Tan; Phone Number: （+86）18974676669
  • Shanxi
    • Yongji, Shanxi, China, 044500
      • Not yet recruiting
      • Yongji Center for Disease Control and Prevention
      • Contact: Yong Yan; Phone Number: （+86）15835919188
    • Yuncheng, Shanxi, China, 043700
      • Not yet recruiting
      • Yuanqu Center for Disease Control and Prevention
      • Contact: Xiaohong Cui; Phone Number: （+86）13903488150
  • Sichuan
    • Mianyang, Sichuan, China, 621000
      • Not yet recruiting
      • Mianyang Youxian District Center for Disease Control and Prevention
      • Contact: gang Xie; Phone Number: （+86）13778031535
    • Neijiang, Sichuan, China, 641000
      • Not yet recruiting
      • Neijiang Shizhong District Center for Disease Control and Prevention
      • Contact: Ling zhong; Phone Number: （+86）18981435233

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experiment group; According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine	Biological: 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha); According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine
Placebo Comparator: placebo; According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo	Biological: placebo; According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Person-years incidence of CIN2+ associated with HPV6/11/16/18.	1 month after 3 doses of vaccine
Person-years incidence of CIN2+ associated with HPV31/33/45/52/58/59/68	1 month after 3 doses of vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Person-years incidence of PI12 and PI6 associated with HPV6/11/16/18 types.		1 month after 3 doses of vaccine
Person-years incidence of PI12 and PI6 associated with HPV31/33/45/52/58		1 month after 3 doses of vaccine
Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68 types associated with CIN2+, CIN1+, PI12 and PI6		1 month after 3 doses of vaccine
Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68-associated anogenital and vaginal lesions (including: genital warts, VIN1+, VaIN1+, and AIN1+).		1 month after 3 doses of vaccine
Person-years incidence of CIN2+, PI12 and PI6 associated with HPV6/11/16/18		After at least 1 dose of vaccine
Person-years incidence of CIN2+, PI12 and PI6 associated with HPV31/33/45/52/58/59/68		After at least 1 dose of vaccine
Person-years incidence of CIN2+, CIN1+, PI12 and PI6 associated with HPV6/11/16/18/31/33/45/52/58/59/68 types.		After at least 1 dose of vaccine
Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68-associated anogenital and vaginal lesions (including: genital warts, VIN1+, VaIN1+, and AIN1+).		After at least 1 dose of vaccine
AE incidence and severity distribution		The first dose of vaccination to within 1 month after the full vaccination
AE incidence and severity distribution		0-30 days after each dose vaccination (including 30 minutes, 0-7 days, 8-30 days)
SAE incidence		During the study，an average of 6 year
Number of pregnant		The first dose of vaccination to within 6 months after the full vaccination
Obtain pregnancy outcomes in pregnant subjects( pregnancy event report form)	Previous pregnancy, current pregnancy mode, neonatal information	The first dose of vaccination to within 6 months after the full vaccination
To evaluate the positive conversion rate of neutralizing antibodies in subjects who completed 3 doses of 11-valent recombinant human papillomavirus vaccine (Hansenula)		7 (1 month after the first dose), 12, 24, 36, 48, 60 and 72 months after the whole course of vaccination
To evaluate the GMT in subjects who completed 3 doses of 11-valent recombinant human papillomavirus vaccine (Hansenula)		7 (1 month after the first dose), 12, 24, 36, 48, 60 and 72 months after the whole course of vaccination

Other Outcome Measures

Outcome Measure	Time Frame
Person-years incidence of PI12 and PI6 associated with HPV59/68	1 month after 3 doses of vaccine
Person-years incidence of PI12 and PI6 associated with HPV59/68	1 month after 1 doses of vaccine

Collaborators and Investigators

• Sponsor: National Vaccine and Serum Institute, China
• Collaborators: Sichuan Center for Disease Control and Prevention; Hunan Provincial Center for Disease Control and Prevention; Centers for Disease Control and Prevention, China; Guangxi Center for Disease Control and Prevention; Simoon Record Pharma Information Consulting Co., Ltd.; Chengdu Institute of Biological Products Co.,Ltd.; Beijing Kantorico Statistical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2022
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HPV Infection HPV vaccine
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Tumor Virus Infections; Pathological Conditions, Signs and Symptoms; Papillomavirus Infections
• Other Study ID Numbers: GXIRB2021-0029-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No