Persistence of Immunity Against Hepatitis B in 12-13 Year Old Adolescents After Infant Hepatitis B Vaccination

Study Overview
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Brief Summary
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This phase IV open study will evaluate the persistence of humoral antibodies against hepatitis B as well as the immune response to a challenge dose of hepatitis B vaccine in adolescents aged 12-13 years, who received three consecutive doses of GSK Biologicals' recombinant hepatitis B vaccine (Engerix™-B) in infancy.

Official Title
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Long-term Persistence of Hepatitis B Antibodies and Immune Response to a Hepatitis B Vaccine Challenge in 12-13 Year Old Adolescents, Vaccinated in Infancy With GlaxoSmithKline (GSK) Biologicals' HBV Vaccine (Engerix™-B)

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Engerix™-B Kinder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Accepted representative (LAR(s)) can and will comply with the requirements of the protocol. A male or female of 12 to 13 years of age at the time of enrolment. With documented evidence of previous vaccination with three consecutive doses of Engerix-B in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age. Written informed consent obtained from the parent(s) or LAR(s) of the subject at the time of enrolment. Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/LAR(s). Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Females of childbearing potential at the time of study entry must have a negative pregnancy test prior to administration of the dose of vaccine and are required to be abstinent or to use adequate contraceptive precautions for one month prior to vaccination. Subjects are required to agree to continue such precautions for two months after vaccination. Exclusion Criteria: 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. Evidence of previous hepatitis B booster vaccination since administration of the third dose of Engerix-B vaccine. History of hepatitis B disease. Hepatitis B vaccination at birth. Adolescents living in institutional care. Planned administration /administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before HBV vaccine challenge and ending 30 days after. Administration of immunoglobulins and/or any blood products within the three months preceding HBV vaccine challenge or planned administration during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the HBV vaccine challenge.. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the challenge dose of study vaccine, or planned use during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Known hypersensitivity to any component of the HBV vaccine or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component. Acute disease and/or fever at the time of enrolment.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Engerix-B Group<br>Subjects who were vaccinated with 3 doses of Engerix-B in infancy and who received a single challenge dose of Engerix-B , intramuscularly in the deltoid region of the non-dominant arm, at 12-13 years of age (Day 0). | Biological: Engerix™-B Kinder<br>* Intramuscular, one dose.<br>* Other names: Engerix™-B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Value | The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL). | One month after the challenge dose (Month 1) | 
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ChemiLuminescence ImmunoAssay (CLIA) Equal to or Above Cut-off Value. | The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL). | One month after the challenge dose (Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | The cut-off values were defined as 3.3 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure. | Before (Day 0) and one month (Month 1) after the challenge dose | 
| Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | The cut-off values were defined as 6.2 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure. | Before (Day 0) and one month (Month 1) after the challenge dose | 
| Number of Subjects With Solicited Local and General Symptoms | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever. Fever was defined as axillary temperature greater than or equal to 37.5 degrees Celsius. | During the 4-day (Day 0-3) follow-up period following the challenge dose vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | 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. | During the 31-day (Day 0-30) follow-up period following the challenge dose vaccination | 
| Number of Subjects With 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. | After the challenge dose of the vaccine (Day 0) up to the study end (Month 1) | 
| Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by ELISA. | Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration equal to or greater than 3.3 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations less than 3.3 mIU/mL) at the pre-challenge dose time point. | One month after the challenge dose (Month 1) | 
| Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by CLIA. | Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration ≥ 6.2 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations < 6.2 mIU/mL) at the pre-challenge dose time point. | One month after the challenge dose (Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adolescent, persistence, HBV, Long-term, Engerix™-B Kinder, Hepatitis B