This Study Aims to Determine the Long-term Persistence of Antibodies Against Hepatitis B and to Evaluate the Immunogenicity and Safety of Hepatitis B Vaccine in Adolescents Vaccinated in Infancy With Infanrix™ Hexa

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 12-13 years who were vaccinated with four doses of Infanrix™-Hexa in infancy and to assess the anamnestic response, immunogenicity, safety and reactogenicity of a single challenge dose of the hepatitis B vaccine Engerix™-B Kinder.

Official Title
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Persistence of Hepatitis B Antibodies, Immunogenicity and Safety of GSK Biologicals' Hepatitis B Vaccine Engerix™-B Kinder (SKF103860) Challenge Dose in Adolescents Vaccinated With Four Doses of Infanrix™ Hexa (SB217744) During Infancy

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' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit). A male or female between the ages of 12 to 13 (from and including the 12th birthday, up to but excluding the 14th birthday) at the time of enrolment. Subjects with documented evidence of previous vaccination with four consecutive doses of Infanrix hexa as part of routine vaccination in Germany: three doses of primary vaccination received by 9 months of age and one booster dose received between 11 and 18 months of age. Written informed consent obtained from the parents/LAR(s) of the subject. In addition to the informed consent that will be signed by the parents/LAR(s), written informed assent of the subject will be sought. 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. 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 series. Exclusion Criteria: Child in care. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccination. Inhaled and topical steroids are allowed. Administration of any chronic drug therapy to be continued during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before and ending 30 days after the HBV challenge dose, with the exception of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (dTpa) vaccine, which can be given as part of routine vaccination practice. 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 (pharmaceutical product or device). Evidence of previous hepatitis B booster vaccination since administration of the fourth dose of Infanrix hexa booster in the second year of life. History of or intercurrent hepatitis B disease. Hepatitis B vaccination at birth. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Family history of congenital or hereditary immunodeficiency. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Major congenital defects or serious chronic illness including thrombocytopenia and bleeding disorders. History of any neurological disorders or seizures. Acute disease and/or fever at the time of enrolment. 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 (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. 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 3 months preceding the dose of study vaccine 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: 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 Kinder Group<br>Subjects who were previously primed and boosted with four doses of Infanrix™ hexa in the first two years of life, received a single dose of Engerix™-B Kinder vaccine. The vaccine was administered intramuscularly into the deltoid of the non-dominant arm. | Biological: Engerix™-B Kinder<br>* Single dose administered intramuscularly in deltoid region of non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HBs Immune Response | Anti-HBs immune response was defined as the number of subjects with Anti-HBs antibody concentrations ≥ 100 mIU/ml. | One month after the single challenge dose of Engerix-B Kinder vaccine (Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HBs Antibody Concentrations at 12-13 Years of Age, After Previous Vaccination With Infanrix Hexa. | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of 6.2 mIU/ml. | Before (PRE) and 1 month after (POST) the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 milli-international units per milliliter (mIU/ml). A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml. | Before the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml and ≥ 10 mIU/ml. | A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 mIU/ml. A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml. | 1 month after the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With an Anamnestic Response to the Single Challenge Dose of Engerix-B Kinder Vaccine. | The amnestic response to the challenge dose was defined as: for initially seronegative subjects, antibody concentration ≥ 10mIU/mL; for initially seropositive subjects, antibody concentration at least four times the pre-challenge antibody concentration. | One month after the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Any Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Any Solicited General Symptoms. | Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature [defined as axillary temperature equal to oe above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | An unsolicited AE covers 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 and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (Day 0-30) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | 
| Number of Subjects With Serious Adverse Events (SAEs). | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Month 0 to Month 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infanrix™ hexa, Hepatitis B antibodies, Immunogenicity, Hepatitis B, Adolescents, Infancy, Engerix™-B Kinder, Safety