Long Term Follow-up Study at Years 2, 3, 4 and 5 Where 2 Dosing Schedules of the Combined Hepatitis A and B Vaccine Were Compared

Study Overview
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Brief Summary
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To evaluate the persistence of anti-hepatitis A virus (HAV) and anti-hepatitis B surface antigen (HBs) antibodies up to 2, 3, 4 and 5 years after administration of the first dose of the study vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Open, randomised, self-contained, multicentric, multinational, long-term antibody persistence studies. Immune persistence was compared between subjects who received either two dose or three doses of GSK Biologicals combined hepatitis A and hepatitis B vaccine. The long-term follow-up studies involved taking blood samples at approximately 2, 3, 4 and 5 years after the primary vaccination of combined hepatitis A and B vaccine to assess antibody persistence. No additional subjects will be recruited during the long term follow-up period.

Official Title
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Evaluate the Persistence of Immune Response of GSK Biologicals' Twinrix™ Vaccine, Administered According to a 0,6 Month Schedule and a 0,1,6 Month Schedule, in Healthy Children Aged Between 1-11 Years at the Time of First Vaccine Dose

Conditions
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Hepatitis B, Hepatitis A

Intervention / Treatment
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* Biological: Twinrix™ Adult
* Biological: Twinrix™ Junior


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in primary study Written informed consent obtained before each long term follow up visit.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 13 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Twinrix Junior<br>Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation). | Biological: Twinrix™ Junior<br>* Intramuscular injection in the left deltoid, 3 doses, junior formulation in primary study.<br>* Other names: Combined hepatitis A and B vaccine;|
| Active Comparator: Twinrix Adult<br>Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation). | Biological: Twinrix™ Adult<br>* Intramuscular injection in the left deltoid, 2 doses, Adult formulation in primary study.<br>* Other names: Combined hepatitis A and B vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-hepatitis A (HAV) Antibody Concentrations | Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL) | Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60) | 
| Anti-hepatitis B (HBs) Antibody Concentrations | Geometric mean concentration for anti-HBs antibodies expressed as Milli-International Units per milliliter (mIU/mL). | Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60) | 
| Anti-HAV Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose. | Any subjects becoming seronegative for anti-HAV antibodies (i.e. titres < 15 mIU/ml) at any long term time point, were to receive an additional vaccine dose administered between 6 to 12 months after Year 5 time point. | Before and one month after additional vaccination | 
| Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose. | Subjects losing seroprotective anti-HBs antibody titres (i.e. titres < 10 mIU/ml) at any long term time point, received an Engerix challenge dose. The table presents the geometric mean concentrations for anti-HBs antibodies, expressed as Milli-International Units per milliliter (mIU/mL). | Before and One month after additional vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy. | A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | From last study visit of the primary study up to Year 5 long term follow-up | 
| Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling at the vaccine injection site. Any= regardless of intensity grade; Grade 3 Pain= spontaneously painful | during the 4-day follow-up period after additional vaccination | 
| Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms. | Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache. Any= regardless of intensity grade or relationship to vaccination; grade 3= prevented normal activity; Related= considered by the investigator to be causally related to the vaccination | During the 4-day follow-up period after additional vaccination | 
| Number of Subjects Receiving an Additional Vaccine Dose and Reporting Unsolicited Adverse Events (AEs). | An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | During the 30-day follow-up period after additional vaccination. | 
| Number of Subjects Receiving an Additional Vaccine Dose and Reporting Any Serious Adverse Events | A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | At least one month after additional vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined hepatitis A and B vaccine, Twinrix™