Long Term Immunogenicity Study of Engerix-B Vaccine in 10 Year Old Children and the Effect of Booster Injections

Study Overview
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Brief Summary
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Hepatitis B immunization has been offered to all grade 4 students (age 9-10) in the province of Quebec, using Engerix-B at a dose of 10 mkg. The peak incidence of hepatitis B occurs between age 15 and 35; the proportion of vaccinated children who will still be protected at this age is currently unknown. This study is designed to determine: persistence of immunity until age 25 persistence of immunological memory as demonstrated by an anamnestic response following a booster dose the effect of a booster dose on immunogenicity at either 5, 10 or 15 years after the primary vaccination course (at age (15, 20 or 25).

Detailed Description
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Three doses of Engerix-B vaccine (10 mkg) were administered according to 0, 1, 6 month schedule to 1126 9-10 year-old children. The primary objective of the study is to evaluate the persistence of antibodies to Engerix-B in all subjects at age 25 and to compare the levels obtained in those given a booster injection at age 15 or 20 with those receiving no booster injection. Secondary objectives To determine the antibody levels obtained following primary vaccination and the proportion of children who seroconvert To determine the antibody levels of one third of subjects at age 15, 5 years after primary vaccination (Group A) To determine the effect on antibody levels of a booster injection at age 15 years given to one third of the subjects (Group A) To determine the antibody levels of subjects in groups A and B at age 20, 5 years after booster (Group A), 10 years after primary vaccination (Group B) To determine the effect on antibody levels of a booster injection at age 20 years given to one third of the subjects (Group B) To determine the effect on antibody levels of a booster injection at age 25 years given to one third of the subjects (Group C) To determine the antibody levels of subjects in Group A and Group B one year after their 5 or 10 year booster To evaluate safety

Official Title
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Open Randomised Clinical Study of the Long Term Immunogenicity of Engerix-B in 10 Year Old Children and of the Effect of Booster Injections Given 5, 10 or 15 Years After Primary Vaccination

Conditions
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Hepatitis B, Vaccination

Intervention / Treatment
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* Biological: Engerix-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously completed the 1995 to 1996 Hepatitis B vaccination program vaccinations (Primary study) to the best of his/her knowledge and already enrolled and followed in the long term study Must be HBc negative Required standard interval between last dose of primary immunization and booster vaccination Written informed consent obtained from the subject Free of obvious health problems as established by medical history and clinical examination before entering into the study Previously completed routine childhood vaccination to the best of his/her knowledge If the subject is female, and the potential of pregnancy exists, it must be asked prior to immunization by the study nurse. According to the protocol d'immunisation du Québec, Engerix-B is not contra-indicated during pregnancy. However, if a participant thinks she could be pregnant (sexually active and no oral contraception or intra uterine device), a pregnancy test will be carried out. In case of pregnancy, the booster vaccination will be performed after delivery. Exclusion Criteria: - Not applicable

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Engerix-B|10 mkg per dose; 3 doses according to 0, 1, 6 month schedule; booster doses 5, 10 or 15 years post-primary vaccination.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the persistence of antibodies to Engerix-B in all subjects at age 25 and to compare the levels obtained in those given a booster injection at age 15 or 20 with those receiving no booster injection. | Long term persistence of anti-HBs and the effect of a booster dose given 5, 10 or 15 years post-primary vaccination. | 1995 - 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - To determine the antibody levels obtained following primary vaccination and the proportion of children who seroconvert | Anti-HBs titers were measured 1 months post-primary vaccination | 1 month post primary vaccination | 
| - To determine the antibody levels of one third of subjects at age 15, 5 years after primary vaccination (Group A) | Anti-HBs titers were measured 5 years post primary vaccination. | 2001 | 
| - To determine the effect on antibody levels of a booster injection at age 15 years given to one third of the subjects (Group A) | The effect of a booster dose was measured | 2001 | 
| - To determine the antibody levels of subjects in groups A and B at age 20, 5 years after booster (Group A), 10 years after primary vaccination (Group B) | Anti-HBs titers were measured 10 years post primary vaccination (Group B) and 5 years post booster dose (Group A) | 2006 | 
| - To determine the effect on antibody levels of a booster injection at age 20 years given to one third of the subjects (Group B) | Anti-HBs titers were measured 1 month post booster dose given 10 years post-primary vaccination | 2006 | 
| - To determine the persistence of antibody 15 years after primary vaccination (Group C) | Anti-HBs titers will be measured | 2011 | 
| - To determine the antibody levels of subjects in Group A and Group B one year after their 5 or 10 year booster | anti-HBs titers will be measured 10 years post booster dose (Group A) and 5 years post booster dose (Group B) | 2011 | 
| - To evaluate the effect of a booster dose given 15 years post primary vaccination (Group C) | Anti-HBs titers will be measured one month post booster dose (Group C) | 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Vaccination, Engerix-B, Immunogenicity, Long-term immunity, Booster dose, Safety