Clinical trial NCT05262010: A Phase III Clinical Trial of a 11-valent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) in Chinese Women Aged 9-45 Years
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HPV InfectioN
HPV-Related Carcinoma
Keywords: HPV Infection HPV vaccine
Lead sponsor: National Vaccine and Serum Institute, China
Sponsor class: INDUSTRY
Collaborators: name: Chengdu Institute of Biological Products Co.,Ltd.
name: Simoon Record Pharma Information Consulting Co., Ltd.
name: Beijing Kantorico Statistical Technology Co., Ltd.
name: Guangxi Center for Disease Control and Prevention
name: Hunan Provincial Center for Disease Control and Prevention
name: Sichuan Center for Disease Control and Prevention
name: Centers for Disease Control and Prevention, China
First posted: 2022-03-02
Enrollment: 13500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 criteria: 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.

Primary outcomes:
measure: Person-years incidence of CIN2+ associated with HPV6/11/16/18.
timeFrame: 1 month after 3 doses of vaccine
measure: Person-years incidence of CIN2+ associated with HPV31/33/45/52/58/59/68
timeFrame: 1 month after 3 doses of vaccine
Secondary outcomes:
measure: Person-years incidence of PI12 and PI6 associated with HPV6/11/16/18 types.
timeFrame: 1 month after 3 doses of vaccine
measure: Person-years incidence of PI12 and PI6 associated with HPV31/33/45/52/58
timeFrame: 1 month after 3 doses of vaccine
measure: Person-years incidence of HPV6/11/16/18/31/33/45/52/58/59/68 types associated with CIN2+, CIN1+, PI12 and PI6
timeFrame: 1 month after 3 doses of vaccine
measure: 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+).
timeFrame: 1 month after 3 doses of vaccine
measure: Person-years incidence of CIN2+, PI12 and PI6 associated with HPV6/11/16/18
timeFrame: After at least 1 dose of vaccine
measure: Person-years incidence of CIN2+, PI12 and PI6 associated with HPV31/33/45/52/58/59/68
timeFrame: After at least 1 dose of vaccine
measure: Person-years incidence of CIN2+, CIN1+, PI12 and PI6 associated with HPV6/11/16/18/31/33/45/52/58/59/68 types.
timeFrame: After at least 1 dose of vaccine
measure: 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+).
timeFrame: After at least 1 dose of vaccine
measure: AE incidence and severity distribution
timeFrame: The first dose of vaccination to within 1 month after the full vaccination
measure: AE incidence and severity distribution
timeFrame: 0-30 days after each dose vaccination (including 30 minutes, 0-7 days, 8-30 days)
measure: SAE incidence
timeFrame: During the study，an average of 6 year
measure: Number of pregnant
timeFrame: The first dose of vaccination to within 6 months after the full vaccination
measure: Obtain pregnancy outcomes in pregnant subjects( pregnancy event report form)
timeFrame: The first dose of vaccination to within 6 months after the full vaccination
measure: To evaluate the positive conversion rate of neutralizing antibodies in subjects who completed 3 doses of 11-valent recombinant human papillomavirus vaccine (Hansenula)
timeFrame: 7 (1 month after the first dose), 12, 24, 36, 48, 60 and 72 months after the whole course of vaccination
measure: To evaluate the GMT in subjects who completed 3 doses of 11-valent recombinant human papillomavirus vaccine (Hansenula)
timeFrame: 7 (1 month after the first dose), 12, 24, 36, 48, 60 and 72 months after the whole course of vaccination
Other outcomes:
measure: Person-years incidence of PI12 and PI6 associated with HPV59/68
timeFrame: 1 month after 3 doses of vaccine
measure: Person-years incidence of PI12 and PI6 associated with HPV59/68
timeFrame: 1 month after 1 doses of vaccine
Locations:
city: Hechi
country: China
facility: Hechi Yizhou District Center for Disease Control and Prevention
state: Guangxi
city: Hezhou
country: China
facility: Hezhou Center for Disease Control and Prevention
state: Guangxi
city: Lianyuan
country: China
facility: Lianyuan Center for Disease Control and Prevention
state: Hunan
city: Qiyang
country: China
facility: Qiyang Center for Disease Control and Prevention
state: Hunan
city: Yongji
country: China
facility: Yongji Center for Disease Control and Prevention
state: Shanxi
city: Yuncheng
country: China
facility: Yuanqu Center for Disease Control and Prevention
state: Shanxi
city: Mianyang
country: China
facility: Mianyang Youxian District Center for Disease Control and Prevention
state: Sichuan
city: Neijiang
country: China
facility: Neijiang Shizhong District Center for Disease Control and Prevention
state: Sichuan
Study officials:
References: