Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years

Study Overview
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Brief Summary
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This phase 3 study will evaluate the immunogenicity and safety of 9-valent HPV recombinant vaccine in Chinese females aged 9 to 45 years

Detailed Description
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This study (protocol 9-HPV-3003) is an immunogenicity and safety study in the subjects (9-19 years of age) who received the 9-valent HPV recombinant vaccine compared with the subjects (20-45 years of age). In this study, we will assess whether the immunogenicity of the 9-valent HPV vaccine given 3-dose schedule in the subjects (9-19 years of age) in noninferior to that in the subjects (20-45 years of age) receiving 3 doses, while assessing the safety of this vaccine.

Official Title
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Evaluating the Immunogenicity and Safety of 9-valent Human Papillomavirus(Type6, 11, 16, 18, 31, 33, 45, 52 and 58) Recombinant Vaccine in Chinese Females Aged 9 to 45 Years: A Phase 3, Open-label, Non-randomised Clinical Trial

Conditions
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CIN2, Vaginal Cancer, CIN1, CIN 3, VaIN1, VaIN2, VaIN3, Genital Wart, VIN 1, VIN 2, VIN 3, AIS, HPV Infections, Cervical Cancer, Vulvar Cancer

Intervention / Treatment
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* Biological: 9-valent HPV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for the first stage: Healthy Chinese females aged 9 to 45 years; Provide legal identification; The subject voluntarily agrees to enroll in this study. If the subject is a minor, both the subject and subject's legal guardian should voluntarily agree to enroll in this study and sign an informed consent form; Be able to understand the study procedures and promise to participate in regular follow-ups under the requirements; Had a negative urine pregnancy test on the day of enrollment, among the subjects of childbearing age; Not in the duration of breast-feeding and no birth plan within 7 months; According to the investigator's judgment that there is no possibility of pregnancy at that time: subjects have taken effective contraception, or asexual life after the last menstrual period, or use IUD, or had undergone ligation; subjects agree to continue take effective contraception such as taking OCS and condom use; No fever symptoms on the day of enrollment (aged> 14 years old, axillary temperature<37.3°C; aged ≤ 14 years old, axillary temperature<37.5°C ); Inclusion Criteria for the second stage: Received all 3 doses of trial vaccination; Subjects aged 9 to 19 years at the first stage. Exclusion Criteria: Received marketed HPV vaccine or plan to receive marketed HPV vaccine during this study period or have enrolled in HPV vaccine clinical trials; History of positive test to HPV, history of cervical cancer (e.g. abnormal screening test results, abnormal cervical biopsy results, including CIN, AIS, and cervical cancer) or history of hysterectomy (vaginal or abdominal radical hysterectomy), or history of pelvic radiotherapy; History of genital diseases related to HPV infection (e.g. uterine peristalsis, VIN, VAIN, AIN, and related cancers); History of STDs, including syphilis, gonorrhea, genital herpes, Mycoplasma genitalium, Lymphgranuloma Venereum, granuloma inguinale, etc.; Known allergy to any vaccine components or history of severe allergic diseases requiring treatment, including shock, laryngeal edema, urticarial, Henoch-Schonlein purpura, Arthus reaction, etc.; Had primary or acquired immunodeficiency such as HIV, SLE, JRA, etc. or received immunosuppressive treatment within one month before study such as long-term glucocorticoid use(≥2mg per kg per day, lasted more than two wks), or plan to receive such treatment from day 0 to month 7 after the last dose; Had chronic diseases or congenital malformations, which might interfere with the process and completion of this study, such as Down Syndrome, heart diseases, liver diseases, chronic diabetes complications, and malignant tumor; Enrolling or plan to enroll in other clinical trials (drug or vaccine); Had infectious diseases such as TB, viral hepatitis, and/or HIV infection; Had convulsions, epilepsy, encephalopathy, and mental illness or family history; With prohibitive contraindications such as Thrombocytopenia or coagulopathy; Asplenic, functionally asplenic, or splenectomy caused by any condition; Within 3 days prior to vaccination, have an acute disease or are in the acute attack of a chronic disease or have used antipyretic, analgesic and anti-allergic drugs (such as: acetaminophen, ibuprofen, aspirin, loratadine, ceti Rizine, etc.); Receipt of inactivated or recombinant vaccines within 14 days, live vaccines within 28 days; Receipt of immune globulin or blood-related products within 3 months; or plan to receive such products during this study period; Had fever symptoms within 24 hours on the first day (aged> 14 years old, axillary temperature ≥ 37.3°C; aged ≤ 14 years old, axillary temperature ≥37.5°C ); Untreated/uncontrolled hypertension before vaccination (aged 9 to 17 years: systolic BP>120mmHg and/or diastolic BP>80mmHg; aged more than 18 years: Systolic BP≥140mmHg and/or diastolic BP ≥90mmHg); Plan to permanently relocate from the area before the end of the study or leave the local area for a long time during the study visit (affecting the scheduled visit time); According to the investigator's judgment, the subject has any condition may interfere with process of evaluation or participating in this study cannot guarantee the object's maximum benefit.

Ages Eligible for Study
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Minimum Age: 9 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9-valent HPV vaccine<br>9-valent HPV recombinant vaccine (Hansenula Polymorpha) All subjects aged 9 to 45 years received 3 doses of 9v HPV vaccine at 0,2,6 month scehdule | Biological: 9-valent HPV vaccine<br>* 9-valent HPV recombinant vaccine (Hansenula Polymorpha) All subjects aged 9 to 45 years received 3 doses of 9v HPV vaccine at 0,2,6 month scehdule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary immunogenicity objective | The primary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the results of seroconversion rate of neutralizing antibodies after immunization in pre-immune negative subjects from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58. | 30 days after the last dose(3 doses schedule) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with postive antibodies after the whole schedule vaccination from the former negative subjects | The secondary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the geometric mean titer (GMT) from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58. | 30 days after the last dose(3 doses schedule) | 
| Rate of seroconversion among the patient aged 9-26 after the whole schedule vaccination | To assess vaccine immunogenicity among the subjects aged between 9 and 26, is the seroconversion rate of neutralizing antibodies and the GMT from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58. | 30 days after the last dose(3 doses schedule) | 
| GMT and seropositive rate of HPV in the 9-19 age group after 60-month follow-up | After receiving all 3 doses vaccinations, the subjects aged 9 to 19 years will be followed for 60 month (Month 12/24/36/48/60) after first vaccination to assess the GMT and seropositive rate (4-fold-increase) to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. | Day 1 to 60 months post vaccination 3 |