Safety and Immunogenicity of a Booster Dose of GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine

Study Overview
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Brief Summary
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In this study, subjects who received primary neonatal vaccination with hepatitis B vaccine at 0, 1, 2, 12 months, 20 years ago in the 103860/272 primary study will be evaluated for immunological memory to hepatitis B vaccine via assessment of the response to a vaccine challenge dose.

Official Title
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Immune Response to a Hepatitis B Vaccine Challenge Dose in Healthy Subjects Who Received Primary Vaccination of GlaxoSmithKline Biologicals' Hepatitis B Vaccine, Approximately 20 Years Ago.

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Engerix™-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. A male or female adult who received the complete neonatal primary vaccination course of hepatitis B vaccine (Engerix™-B), in the 103860/272 primary study approximately 20 years earlier. Documented level of anti-HBs antibody concentrations < 100 milli-international units per milliliter (mIU/ml) at the previous long-term time-point for which serological results are available for that subject. Written informed consent obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the hepatitis B challenge dose. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the hepatitis B vaccine challenge dose. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before the hepatitis B vaccine challenge dose and ending 30 days after. Subjects who received a booster dose of hepatitis B vaccine outside the context of this study between the long-term time-point at the documented level of anti-HBs antibody concentrations and the current challenge dose study visit. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. Acute disease at the time of enrolment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Administration of immunoglobulins and/or any blood products within the three months preceding the hepatitis B vaccine challenge dose or planned administration during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.
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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Neonates from mother HBsAg (+) and HBeAg (+) had received HBV vaccine at Month 0, 1, 2, 12, 60 (5 doses) | Biological: Engerix™-B<br>* A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.<br>|
| Experimental: Group 2<br>Neonates from mother HBsAg (+) and HBeAg (+) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses) | Biological: Engerix™-B<br>* A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.<br>|
| Experimental: Group 4<br>Neonates from mother HBsAg (+) and HBeAg (-) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses) | Biological: Engerix™-B<br>* A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.<br>|
| Experimental: Group 6<br>Neonates from mother HBsAg (-) and HBeAg (-) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses) | Biological: Engerix™-B<br>* A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With an Immune Response to a Challenge Dose of Hepatitis B Vaccine | Immune response to a challenge dose of hepatitis B vaccine is defined as at least a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive (≥ 3.3 mIU/mL) at the previous available long-term time point, or a post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in subjects seronegative (<3.3 mIU/mL) at the previous available long-term time point. | One month after the hepatitis B vaccine challenge dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values | Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL. | One month after the hepatitis B vaccine challenge dose | 
| Concentration of Anti-HBs Antibodies | Concentrations are given as Geometric Mean Concentrations (GMCs), calculated on subjects seropositive (subjects with anti-HBs antibody concentrations ≥ 3.3 mIU/mL) post-challenge dose. | One month after the hepatitis B vaccine challenge dose | 
| Number of Subjects Reporting Unsolicited Adverse Events | 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 31-day follow-up period after the challenge dose of hepatitis B vaccine | 
| Number of Subjects Reporting Serious Adverse Events | A serious adverse event 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 31-day follow-up period after the challenge dose of hepatitis B vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis, vaccine