Efficacy and Immunogenicity Study of Recombinant Human Papillomavirus Bivalent（Type 16/18 ）Vaccine

Study Overview
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Brief Summary
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This is a Phase III clinical trial of the novel recombinant HPV 16/18 bivalent vaccine manufactured by Xiamen Innovax Biotech CO., LTD. The primary objective of this study is to demonstrate the efficacy of the vaccine against relevant outcomes in healthy women above 18 years old at enrolment. The secondary objectives are to evaluate the safety, immunogenicity and immuno-persistence of the vaccine. Meanwhile, this study tries to compare the difference of safety and immunogenicity among different lots. Approximately 6000 study subjects will be enrolled and randomly stratified into 2 groups and receive human papillomavirus (HPV) vaccine(three different lots) or commercialized hepatitis E vaccine(Hecolin) according to a 0-1-6 month schedule.

Official Title
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A Phase III Multicenter, Randomized, Double-Blind, Placebo(Hepatitis E Vaccine)Controlled Study to Evaluate the Efficacy, Immunogenicity and Safety of a Recombinant(E.Coli)Human Papillomavirus Bivalent Vaccine in Healthy Women

Conditions
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Cervical Intraepithelial Neoplasia, Cervical Cancer, Vaginal Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Persistent Infection

Intervention / Treatment
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* Biological: HPV Vaccine
* Biological: HEV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects between, and including, 18 and 45 years of age at the first vaccination; Healthy subjects as established by medical history and history-oriented clinical examination; Be able to understand and comply with the request of the protocol; Without acute cervicitis; Not pregnant; Have intact cervix. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine)within 30 days preceding the first vaccination, or plan to use during the study period; Are using immunosuppressants; Administration of immunoglobulin and/or any blood products within the three months preceding the first vaccination or planned administration during the study period; Vaccinated of inactivated vaccine 14 days or attenuated vaccine 21 days before the enrollment; Fever; Concurrently participating another clinical trial; Has received vaccines against HPV 16/18 ; Immunodeficient; History of allergic disease; Serious medical disorders; Blood coagulation disorders; Epilepsy; Unable to comply with protocol due to the mental illness; Visible Condyloma; Pregnant or breast-feeding women; vergins; Have more than 4 sexual partners.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV vaccine<br>This dosage contains 40μg HPV 16 virus-like particle antigen and 20μg HPV 18 virus-like particle antigen adsorbed in alum-adjuvant | Biological: HPV Vaccine<br>* 3 doses at month 0,1 and 6<br>|
| Placebo Comparator: HEV vaccine<br>commercialized HEV vaccine which contains 30μg HEV antigen adsorbed in alum-adjuvant | Biological: HEV vaccine<br>* 3 doses at month 0,1 and 6<br>* Other names: Hecolin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Histopathologically-confirmed CIN2+ and/or VIN2+ and/or VaIN2+ Associated With HPV-16 and/or -18 Cervical Infection |  | expected 5-6 years | 
| Number of Subjects With HPV-16 and/or -18 persistent cervical infection(6-month+ definition) |  | expected 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Local and General Symptoms |  | Within 7 days after each vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events |  | Month 7 | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) |  | expected 5-6 years | 
| number of subjects with persistent cervical infection (12-month+ definition)associated with HPV-16 and/or HPV-18 |  | expected 5-6 years | 
| number of subjects Histopathologically-confirmed CIN1+ and/or VIN1+ and/or VaIN1+ associated with HPV-16 and/or -18 cervical infection |  | expected 5-6 years | 
| number of subjects with incidence infection associated with HPV-16 and/or HPV-18 |  | expected 2-3 years | 
| Anti-HPV16 and anti-HPV18 seroconversion rates and geometric mean concentrations at Months 7 |  | month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, Human Papillomavirus 16, Human Papillomavirus 18, Cervical Intraepithelial Neoplasia, cervical Cancer, Vaginal intraepithelial neoplasia, Vulvar intraepithelial neoplasia