Efficacy and Immunomodulation Study of Simultaneous Human Papillomavirus/ Hepatitis B (HPV/HBV) Vaccination

Study Overview
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Brief Summary
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Rationale: In march 2009 the Dutch Health Council advised to introduce general infant hepatitis B (HBV) vaccination in the Dutch national immunization program (NIP) {Gezondheidsraad 2009 #16914}. To reach the anticipated health benefits earlier, a catch-up vaccination in pre-adolescents should complement the program, for girls preferably combined with human papillomavirus (HPV) vaccination at the age of 12 years. Although the rationale is clear, particular aspects of combining HPV and HBV vaccination deserve further attention, especially as it has been shown that combining HPV and HBV vaccination results in reduced HBV immunogenicity/seroresponses {Wheeler, Bautista, et al. 2008 #17284}{Pedersen 2009 #16684}. The reason for this interference is unknown, but might be due to concomitant use of different antigens and/or adjuvants, possibly skewing immunity in opposite directions. Despite proven immunostimulatory effects, the use of (new) adjuvants has raised safety concern among the general public as well {Israeli, Agmon-Levin, et al. 2009 #16924}. Objective, Study design and Study population: In view of the observations and concerns mentioned above, further investigation into interference of HPV and HBV vaccination and adjuvant use is justified. In this context RIVM propose to study single vs simultaneous HBV and HPV vaccination in 11-12-year-old girls while monitoring antigen-related and antigen-unrelated immunological parameters. The anticipated results will elucidate the extent of interference between simultaneous HPV and HBV vaccination in the target group, and guide the choice for a HBV vaccine and schedule when the HBV catch-up program is indeed introduced. Furthermore, specific immunological trends post single and combined HPV and HBV vaccination will be elucidated, increasing the investigators comprehension of adjuvant use.

Official Title
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A Phase 4, Randomized, Open Label Clinical Trial to Determine Efficacy and Immunomodulation of Simultaneous HPV/HBV Vaccination Tango-trial)

Conditions
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Human Papillomavirus Infection

Intervention / Treatment
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* Biological: Cervarix
* Biological: Engerix-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female pre-adolescents born in 1998, eligible for HPV vaccination in 2011. Able to fulfill all study requirements. Exclusion Criteria: Previous vaccination with any licensed or experimental HPV or HBV vaccine. Contraindication for vaccination with Cervarix®. Contraindication for vaccination with Engerix-B®. Use of investigational vaccine or medication within 30 days before study History of severe adverse reaction associated with a vaccine or vaccine component. Heart disease Liver disease Spleen removal Asthma Immune deficiency or suppression

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV&HBV vaccin<br>HPV&HBV vaccin | Biological: Cervarix<br>* Cervarix, HPV vaccin<br>Biological: Engerix-B<br>* Engerix-B, HBV vaccin<br>|
| Experimental: HPV vaccination<br>HPV vaccination | Biological: Cervarix<br>* Cervarix, HPV vaccin<br>|
| Experimental: HBV vaccination<br>HBV vaccination | Biological: Engerix-B<br>* Engerix-B, HBV vaccin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody seroprotection proportion for HBV in groups 1, 2 and 3 measured in Sample 2. |  | Month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1998 female birth cohort eligible for HPV vaccination in 2011 within the Dutch NIP