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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HPV InfectioN, HPV-Related Carcinoma

Intervention / Treatment
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* Biological: 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - non-gynecological related *Chinese women with a history of sexual life who are 18-45 years old at the time of enrollment and can provide legal identification; *Axillary body temperature <37.3℃ on the day of enrollment; The subjects themselves have the ability to understand the clinical trial and voluntarily sign the informed consent; 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; No previous HPV vaccination history, no commercially available HPV vaccine during the study period (about 6 years after enrollment) plan of; The subject has a negative urine pregnancy test on the day before vaccination. - Gynecology related *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. *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 * Those with abnormal blood pressure (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) on physical examination before vaccination; *3 months prior to vaccination or planned to receive any immune globulin or blood products within 7 months of enrollment; *Received any vaccine within 14 days prior to vaccination, or received live vaccine within 28 days; *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.); 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.); 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; 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; Previous splenectomy or impaired spleen function; Those with previous or current severe liver, kidney and cardiovascular diseases, complicated diabetes, and malignant tumors; Have a history of epilepsy, convulsions, mental illness or a family history of mental illness; Suffering from thrombocytopenia or any coagulation disorder that can become a contraindication to intramuscular injection; Participate in other clinical studies (drugs, vaccines and medical devices) within 3 months before vaccination or during the planned study period; 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 *Pregnant, breastfeeding, or within 6 weeks of pregnancy at the time of the first dose of the vaccine; *The subject is in the menstrual period; *Acute lower genital tract infection (such as acute vulvitis/vaginitis/cervicitis, etc.) found by the naked eye during gynecological examination; 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.); 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.); 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experiment group<br>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)<br>* According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine<br>|
| Placebo Comparator: placebo<br>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<br>* According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV Infection HPV vaccine