Effectiveness of Single Dose or Two Doses of Bivalent HPV Vaccine in Thailand

Study Overview
=================
Brief Summary
-----------------
This is a community intervention effectiveness study in female school students in Thailand. The study objectives are: To demonstrate HPV vaccine effectiveness of Single Dose (SD) by a reduction in vaccine-type HPV prevalence (HPV 16 and HPV 18) at Year 2 and Year 4 post vaccination compared to unvaccinated same grade female students To demonstrate that HPV vaccine effectiveness of SD and two-dose (2D) regimens are similar by comparing reductions in vaccine type prevalence at Year 2 and Year 4 post vaccination compared with the baseline surveys in the two provinces

Detailed Description
-----------------
The study will investigate the effectiveness of a SD of HPV vaccine through the conduct of a regional effectiveness study in Thailand. The study will be conducted in schools and district hospitals from the two selected provinces (Udon Thani and Buriram) The study design includes 4 distinct and independent components: 1) vaccination, 2)baseline cross-sectional survey, 3,4)sequential cross-sectional surveys for impact assessments at Year 2 and Year 4 post vaccination. Vaccination: The target population is represented by all Grade 8 female students in the two provinces. All enrolled students will receive either SD (Udon Thani) or 2D (Buriram). A subset (N=200/province) of Grade 8 female students in each province will be selected for a blood collection before vaccination for assessment of vaccine immunogenicity. Surveys (baseline, Year 2 and Year 4 impact surveys): Target populations of are a subset of female students of Grades 10 High school (HS)/year 1 Vocational School (VS) and Grade 12 HS/year 3 VS from all schools in the two provinces and the sampling unit is an individual. Urine collection will be performed to assess HPV infection by DNA PCR and for genotyping of positive samples. A subset of students (N=200 per province) will be randomly selected for each of the Year 2 and Year 4 surveys for blood collection for assessment of vaccine immunogenicity. Demographics and sexual behavior questionnaire will be collected from all students.

Official Title
-----------------
A Community Intervention Effectiveness Study: Single Dose or Two Doses of Bivalent HPV Vaccine (CERVARIX) in Female School Students in Thailand

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Biological: Bivalent HPV vaccine CERVARIX®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria A. Grade 8 (Mathayom 2): Female students with identification card Less than 15 years of age Parent or guardian consent for vaccination and blood collection as applicable Participant assent for vaccination, questionnaire, and blood collection as applicable B. Baseline survey (Grade 10 / year 1, Grade 12 / year 3) 1. Female students with identification card Participant assent for questionnaire and urine collection C. Year 2 post vaccination survey( Grade 10 / year 1) Year 4 post vaccination survey (Grade 12 / year 3) Female students with identification card Parent or guardian consent for blood collection as applicable Participant assent for questionnaire, urine and blood collection from those vaccinated at Grade 8 as applicable Exclusion criteria A. Grade 8 (Mathayom 2): Students who already received HPV vaccination Reported pregnancy Any student who has a preexisting known medical condition or diagnosed psychological illness which in the opinion of the Principal Investigator or designee may be detrimental to her wellbeing B. Baseline survey (Grade 10 / year 1, Grade 12 / year 3) 1. Any student who has a preexisting known medical condition or diagnosed psychological illness which in the opinion of the Principal Investigator or designee may be detrimental to her wellbeing C. Year 2 post vaccination survey( Grade 10 / year 1) Year 4 post vaccination survey (Grade 12 / year 3) 1. Any student who has a preexisting known medical condition or diagnosed psychological illness which in the opinion of the Principal Investigator or designee may be detrimental to her wellbeing

Ages Eligible for Study
-----------------
Minimum Age: 13 Years
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Age range of subjects: 13 up to 18 years of age Vaccination - grade 8: 13 to less than 15 years of age Behavioral questionnaire: grade 8 (as above) and 15-18 years of age for baseline (unvaccinated) and Year 2 and Year 4 cross-sectional surveys post vaccination Urine collection: 15-18 years of age for baseline (unvaccinated) and Year 2 and Year 4 cross-sectional surveys post vaccination Blood collection: grade 8 (as above) and 15-18 years of age for Year 2 and Year 4 cross-sectional surveys post vaccination
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Cross-sectional baseline survey<br>This are will collect behavioral questionnaire and urine in Grade 10 high school and Year 1 vocational school and Grade 12 high school and Year 3 Vocational school female students | |
| Active Comparator: Single Dose HPV vaccination<br>Grade 8 female students from Udon Thani Province This arm will collect behavioral questionnaire and blood prior vaccination Intervention: Single Dose HPV Vaccination with CERVARIX®(Glaxo Smith Kline, GSK, Rixensart, Belgium) | Biological: Bivalent HPV vaccine CERVARIX®<br>* Bivalent HPV vaccine(Glaxo Smith Kline, GSK, Rixensart, Belgium) presented as a suspension for intramuscular injection containing purified viral L1 protein for HPV types 16 and 18. Each 0.5 mL dose of the bivalent vaccine contains 20μg of HPV-16 L1 protein and 20 μg of HPV-18 L1 protein adsorbed onto a proprietary adjuvant system containing 500 μg of aluminum hydroxide and 50 μg of 3-O-desacyl-4-monophosphoryl lipid A (AS04)<br>|
| Active Comparator: Two-dose HPV vaccination<br>Grade 8 female students from Buriram Province This arm will collect behavioral questionnaire and blood prior vaccination Intervention: Two-Dose HPV Vaccination with CERVARIX®(Glaxo Smith Kline, GSK, Rixensart, Belgium) | Biological: Bivalent HPV vaccine CERVARIX®<br>* Bivalent HPV vaccine(Glaxo Smith Kline, GSK, Rixensart, Belgium) presented as a suspension for intramuscular injection containing purified viral L1 protein for HPV types 16 and 18. Each 0.5 mL dose of the bivalent vaccine contains 20μg of HPV-16 L1 protein and 20 μg of HPV-18 L1 protein adsorbed onto a proprietary adjuvant system containing 500 μg of aluminum hydroxide and 50 μg of 3-O-desacyl-4-monophosphoryl lipid A (AS04)<br>|
| No Intervention: Cross-sectional survey at Year 2<br>This arm will collect behavioral questionnaire, urine and blood in Grade 10 high school and Year 1 vocational school female students | |
| No Intervention: Cross-sectional survey at Year 4<br>Cross-sectional survey at Year 4 post vaccination | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPV infection prevalence | HPV DNA PCR in urine | Baseline survey (unvaccinated students) during the first year of the study | 
| HPV infection prevalence | HPV DNA PCR in urine | Year 2, two years post vaccination | 
| HPV infection prevalence | HPV DNA PCR in urine | Year 4, four years post vaccination | 
| Identification of HPV circulating strains | HPV genotyping on urine positive samples | Baseline survey (unvaccinated students) during the first year of the study | 
| Identification of HPV circulating strains | HPV genotyping on urine positive samples | Year 2, two years post vaccination | 
| Identification of HPV circulating strains | HPV genotyping on urine positive samples | Year 4, four years post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPV type-specific antibody response prior and post vaccination | Blood Sample | Prior vaccination and at Year 2 and Year 4 Post vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Effectiveness, CERVARIX, Urine, DNA PCR, HPV infection, HPV genotyping