Dose-Ranging Study of Recombinant Human Papillomavirus Virus 16/18 Bivalent Vaccine

Study Overview
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Brief Summary
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This is a phase II clinical study of the novel recombinant HPV 16/18 bivalent vaccine expressed in E. coli. The primary purpose of this study is to evaluate which dosage of the HPV vaccine can induce higher antibody and at the same time caused less adverse events. The secondary purpose of this study is to to evaluate the safety and immunopersistence of the study vaccine.

Detailed Description
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Totally 1600 healthy women of 18-25 years of age were enrolled. The participants were randomly stratified into 4 groups and receive different dosage of human papillomavirus (HPV) vaccine or placebo administered intramuscularly according to a 0-1-6 month schedule. The women were actively monitored for adverse events for 1 month after each injection. Severe adverse events during the trial were followed up. Serum samples from all the subjects would be collected on day 0, 7m, 24m, 48m and 72m to evaluate the immunogenicity and immuno-persistency.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Dose-Ranging Study of Recombinant Human Papillomavirus Virus 16/18 Bivalent Vaccine (E.Coli)in Healthy Female Subjects Aged 18 to 25 Years

Conditions
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Cervical Intraepithelial Neoplasia, Cervical Cancer

Intervention / Treatment
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* Biological: 30μg HPV
* Biological: 60μg HPV
* Biological: 90μg HPV
* Biological: Hepatitis B vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent from the subject prior to enrolment; Female between, and including, 18 and 25 years of age at the time of enrolment; Subjects must be free of obvious health problems; Not pregnant and having no plan for pregnancy; Exclusion Criteria: Pregnant or breastfeeding or having plan for pregnancy during the whole study (Month 0-7); Previous vaccination against HPV; Having severe allergic history or other immunodeficiency; Chemotherapy and other immunosuppressive agents using;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 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: 30μg HPV<br>Participants in this arm would receive 30μg HPV vaccines which contains 20μg HPV 16 antigen and 10μg HPV 18 antigen | Biological: 30μg HPV<br>* Participants would intramuscularly receive 30μg of HPV 16/18 bivalent vaccine at 0, 1, 6 month for 3 doses.<br>|
| Experimental: 60μg HPV<br>Participants in this arm would receive 60μg HPV vaccines which contains 40μg HPV 16 antigen and 20μg HPV 18 antigen | Biological: 60μg HPV<br>* Participants would intramuscularly receive 60μg of HPV 16/18 bivalent vaccine at 0, 1, 6 month for 3 doses.<br>|
| Experimental: 90μg HPV<br>Participants in this arm would receive 90μg HPV vaccines which contains 60μg HPV 16 antigen and 30μg HPV 18 antigen | Biological: 90μg HPV<br>* Participants would receive 90μg HPV vaccines which contains 60μg HPV 16 antigen and 30μg HPV 18 antigen<br>|
| Placebo Comparator: hepatitis B vaccine<br>Participants in this arm would receive hepatitis B vaccine. | Biological: Hepatitis B vaccine<br>* Participants would intramuscularly receive 10μg of hepatitis B vaccine at 0, 1, 6 month for 3 doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion of anti-HPV 16 and anti-HPV 18 neutralizing antibody | To detect the anti-HPV 16 and anti-HPV 18 neutralizing antibody level on day 1 and one month after dose 3. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | All the adverse events in one month after each dose would be recorded in the diary card. All the Serious Adverse Events(SAE) occurred during clinical trial time frame would be recorded. | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Papilloma Virus 16, Human Papilloma Virus 18, vaccine, Cervical Intraepithelial Neoplasia, cervical Cancer