Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Injected According to a 0, 12-month Schedule

Study Overview
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Brief Summary
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The aim of this study is to evaluate the persistence of hepatitis A antibodies at 138, 150, 162, 174,186, 198, 210, 222, 234 and 246 months after subjects received their first dose of a 2 dose vaccination schedule of hepatitis A vaccine. This protocol posting deals with objectives & outcome measures of the extension phase at year 11 to 20. No additional subjects will be recruited during this long-term follow-up.

Detailed Description
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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. Months 138, 150, 162, 174,186, 198, 210, 222, 234 and 246), 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 extend the follow up until Year 20. The study has 10 phases: 100571, 100572, 100573, 100574, 100575, 110677, 110678, 110679, 110680, 110681.

Official Title
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Double-blind Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Two Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 12 Month Schedule in Healthy Adult Volunteers

Conditions
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Hepatitis A

Intervention / Treatment
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* Biological: Havrix™


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 29 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Havrix Group<br>Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12. | Biological: Havrix™<br>* 2 doses at 12 months interval<br>|

What is the study measuring?
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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). ** = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246. | At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246 | 
| Number of Seropositive Subjects Against Hepatitis A Virus | A seropositive subject was a vaccinated subject whose concentrations for antibodies against hepatitis A virus (anti-HAV) were equal or above (>=) the assay cut-off for seropositivity of 15 milli-international units per milliliter (mIU/mL). ** = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246. | At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as GMC expressed as mIU/mL. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198. Please note that value 14.9 means <15. | Before additional vaccination, 14 days after additional vaccination and 30 days after additional vaccination | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Additional vaccination was given to 4 subjects at the Month 186 timepoint and to 1 subject at the Month 198 timepoint. | During the 4-day (Days 0-3) follow-up period after additional vaccination | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198. | During the 4-day (Days 0-3) follow-up period after additional vaccination | 
| Number of Subjects Reporting 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. 4 subjects received additional vaccination at Month 186 and 1 at Month 198. | During the 30-day follow-up period after additional vaccination | 
| Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine 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 | At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246 | 
| Number of Subjects Reporting Serious Adverse Events (SAE) After Additional Vaccination | 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. 4 subjects received additional vaccination at Month 186 and 1 at Month 198. | During the 30-day follow-up period after additional vaccination | 
| Number of Subjects Reporting Pregnancies After Additional Vaccination | The number of subjects with outcome of pregnancies reported among subjects who had received the additional vaccination was tabulated. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198. | At Months 186 and 198 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAVRIX™, Hepatitis A