Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term persistence of immunity to hepatitis B in adolescents aged 15-16 years who were vaccinated with Engerix™-B Kinder in infancy. The study will also assess the immune response to a challenge dose of Engerix™-B Kinder in these subjects.

Detailed Description
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This MDD has been updated following the Protocol Amendment 1, dated 20 June 2013. The Protocol was amended because GSK replaced its in-house Enzyme-Linked ImmunoSorbent Assay (ELISA) that was used to measure anti-HBs (antibodies to Hepatitis B surface antigen) antibody concentrations with ChemiLuminescence ImmunoAssay (CLIA). Additionally, the threshold level of prednisone was modified to reflect the dosage normally prescribed to adolescents.

Official Title
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Long-term Persistence of Hepatitis B Antibodies and Immune Response to a Challenge Dose of GSK Biologicals' Hepatitis B Virus Vaccine, Engerix™-B Kinder (SKF103860), in 15-16 Years Old Adolescents, Vaccinated in Infancy With Engerix™-B Kinder

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: Subject's parent(s)/guardians who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. A male or female between, and including, 15 and 16 years of age at the time of the vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. 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. Documented evidence of previous vaccination with three consecutive doses of Engerix™-B Kinder in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Previous hepatitis B vaccination since administration of the third dose of Engerix™-B Kinder. History of hepatitis B disease. Administration of a vaccine not foreseen by the study protocol within the period starting 30 days before study vaccine dose, or planned administration during the study period. 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 vaccine/product. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease and/or fever at the time of enrollment. Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the 3 months preceding the study vaccine dose 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: 15 Years
Maximum Age: 16 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: HBV Group<br>Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Engerix™-B Kinder<br>* Single dose administered intramuscularly in the deltoid region of non-dominant arm at Day 0.<br>|

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 Equal to or Above the 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-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL. | Before (Day 0) and one month after the challenge dose (Month 1) | 
| Antibody Titers Against Hepatitis B Virus | Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs. | Before (Day 0) and one month (Month 1) after the challenge dose | 
| Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. | Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to ) 4-fold rise in post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point | Prior to vaccination with the challenge dose | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. >50 mm. | During the 4-day (Days 0-3) follow-up period after the challenge dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C | During the 4-day (Days 0-3) follow-up period after the challenge dose | 
| Number of Subjects Reporting 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) follow-up period after the challenge dose | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | Serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. | During the entire study period (Day 0 to Month 1) | 

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