Immune Response of Healthy Subjects Who Received Neonatal Vaccination Course With Engerix™-B Vaccine.

Study Overview
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Brief Summary
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This study will evaluate the immune response of healthy subjects who received neonatal vaccination course with GSK Biologicals' Engerix™-B vaccine, approximately 20 years ago. The presence of immune memory against hepatitis B surface antigen (HBsAg) in these subjects will be investigated by the administration of a challenge dose of hepatitis B vaccine and the comparison of their antibody concentration before and one month after vaccination. This protocol posting deals with objectives & outcome measures of the booster phase. No new subjects will be recruited during this booster phase of the study.

Official Title
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Study to Evaluate the Immune Response of Healthy Subjects Who Received Neonatal Vaccination Course With GSK Biologicals' Engerix™-B Vaccine, Approximately 20 Years Ago.

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: EngerixTM-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 who received the complete neonatal primary vaccination course of Engerix™-B in the 103860/273 primary study approximately 20 years earlier. Anti-HBs antibody concentrations less than the specified value at the last available follow-up time-point. 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 vaccination. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the Engerix™-B challenge dose, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressant or other immune-modifying drugs within six months prior to challenge dose administration. Planned administration/ administration of a vaccine not foreseen by the study protocol starting from 30 days before the challenge dose and ending 30 days after. Administration of a hepatitis B vaccine outside the context of this study between the follow-up time-point at which anti-HBs antibody concentrations was less than the specified value 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. Acute disease at the time of enrolment. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. 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 challenge dose visit or planned administration during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 22 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Engerix(4-dose)+HepatitisB(HB) Immunoglobulin (Ig)<br>Subjects who previously received HBV vaccine at 0, 1, 6 and 60 months (4 doses) and HBIg concomitantly at Month 0, and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study. | Biological: EngerixTM-B<br>* Intramuscular injection, one dose.<br>|
| Experimental: Engerix(3-dose)+HBIg<br>Subjects who previously received HBV vaccine at 0, 1, 6 months (3 doses) and HBIg concomitantly at Month 0, and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study. | Biological: EngerixTM-B<br>* Intramuscular injection, one dose.<br>|
| Experimental: Engerix(4-dose)<br>Subjects who previously received HBV vaccine at 0, 1, 6 and 60 months (4 doses) and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study. | Biological: EngerixTM-B<br>* Intramuscular injection, one dose.<br>|
| Experimental: Engerix(3-dose)<br>Subjects who previously received HBV vaccine at 0, 1, 6 months (3 doses) and received a challenge dose of HBV vaccine after approximately 20 years (noted as Day 0) in the current study. | Biological: EngerixTM-B<br>* Intramuscular injection, one dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With an Anamnestic Response to a Challenge Dose of Hepatitis B Virus (HBV) Vaccine as Measured by Enzyme-Linked Immunosorbent Assay (ELISA). | Anamnestic response to the challenge dose is defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge anti-HBsAg antibody concentrations in subjects seropositive at the last available follow-up time-point. -Post-challenge dose anti-HBsAg antibody concentrations >= 10 mIU/mL in subjects seronegative at the last available follow-up time-point. | One month after the hepatitis B vaccine challenge dose. | 
| Number of Subjects With an Anamnestic Response to a Challenge Dose of Hepatitis B Virus (HBV) Vaccine as Measured by ChemiLuminescence ImmunoAssay (CLIA). | Anamnestic response to the challenge dose is defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge anti-HBsAg antibody concentrations in subjects seropositive at the last available follow-up time-point. -Post-challenge dose anti-HBsAg antibody concentrations >= 10 mIU/mL in subjects seronegative at the last available follow-up 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-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by ELISA. | Cut-off values assessed were as follows: ≥3.3 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL | One month after the hepatitis B vaccine challenge dose. | 
| Number of Subjects With Anti-Hepatitis B Surface (HBs) Antibody Concentrations Above Cut-off Values as Measured by CLIA. | Cut-off values assessed were as follows: ≥6.2 milli-international units/milliliter (mIU/mL), ≥10 mIU/mL, ≥100 mIU/mL | One month after the hepatitis B vaccine challenge dose. | 
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ELISA. | Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL). | One month after the hepatitis B vaccine challenge dose. | 
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by CLIA. | Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL). | One month after the hepatitis B vaccine challenge dose. | 
| Number of Subjects Experiencing Any, Grade 3 and Related to Vaccination Unsolicited Symptoms. | Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Grade 3 symptom is any event that prevented normal activities. Related symptom is an event that was considered by investigator as causally related to the study vaccination. | During the 31-day follow-up period after the hepatitis B vaccine challenge dose. | 
| Number of Subjects That Experienced Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | During the entire study period after the challenge dose (1 month). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Engerix-B, Hepatitis B