Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine, Injected According to 0, 6-month Schedule

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the long-term persistence of hepatitis A antibodies at 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years after subjects received their first dose of a 2 dose vaccination schedule of hepatitis A vaccine.

Detailed Description
-----------------
This is a long-term follow-up study at Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after primary vaccination with GSK Biologicals' hepatitis A vaccine (two-dose schedule). To evaluate the long-term antibody persistence, volunteers will donate a blood sample at Years 11, 12, 13, 14,15, 16, 17, 18, 19 and 20 after the first vaccine dose of the primary vaccination course to determine their anti-hepatitis A (anti-HAV) antibody concentrations If a subject has become seronegative for anti-HAV antibodies during any of the long-term blood sampling time point (i.e. Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years), he/ she will be offered an additional vaccine dose. A blood sample will be taken on the day of the additional vaccination, 14 days and one month after additional vaccination to evaluate the immune response following this vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007 and to include an extended follow up period up to Year 20 after primary vaccination. The study has 10 phases (100576, 100577, 100578, 100579, 100580, 111028, 111029, 111030, 111031, 111032).

Official Title
-----------------
Double-blind, Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 6 Month Schedule in Healthy Adult Subjects

Conditions
-----------------
Hepatitis A

Intervention / Treatment
-----------------
* Biological: Havrix™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who had received at least one dose of the study vaccine in the primary study Written informed consent will have been obtained from the subjects before the blood sampling visit of each year.

Ages Eligible for Study
-----------------
Minimum Age: 29 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Havrix Group<br>Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up. | Biological: Havrix™<br>* 2 doses at 6 months interval<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination | 
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as GMC expressed as mIU/mL. | Before the additional dose, 14 days and 30 days after the additional dose | 
| Number of Seropositive Subjects for Anti-HAV Antibodies. | Seropositivity for anti-HAV antibodies defined as antibody concentrations ≥ 15 mIU/mL for Year 11 to Year 20 time points. The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | From Year 11 to Year 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy | An 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 | Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain = symptom that prevented normal activities. Grade 3 redness and swelling = redness or swelling above 30 mm and persisting more than 24 hours. Any = incidence of a particular symptom regardless of intensity. | During the 4-day (Day 0-3) follow-up period after additional vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed included fatigue, fever, gastrointestinal symptoms, and headache. | During the 4-day (Day 0-3) follow-up period after additional vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) | An AE 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. Grade AE = produced significant impairment of functioning or incapacitation and was a definite hazard to the subject's health. Related AE = assessed by the investigator as related to the study vaccination. | During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15) | 
| Number of Subjects Reporting Serious Adverse Events (SAE) | An 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. | During the follow-up period after additional vaccination up to Year 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Havrix™, Hepatitis A