Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children

Study Overview
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Brief Summary
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This study will evaluate the persistence of immunity to hepatitis B in healthy children aged 7 to 8 years, after previous vaccination with Infanrix hexa™ in the first two years of life, and also their ability to mount an immune response to the challenge dose of Engerix-B™ Kinder.

Official Title
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Long-term Antibody Persistence of Hepatitis B Antibodies and Immune Response to a Hepatitis B Vaccine (Engerix-B Kinder) Challenge in Children Previously Vaccinated With Infanrix Hexa Vaccine

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 Acceptable Representative(s) can and will comply with the requirements of the protocol. A male or female 7 to 8 years of age 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/Legally Acceptable Representative(s) of the subject at the time of enrolment. In addition to the informed consent that will be signed by the parent(s)/Legally Acceptable Representative(s), written informed assent of the subject will be sought when the subject is judged able to understand by the investigator. Healthy subjects as established by medical history and clinical examination before entering into the study. 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. 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 fourth dose of Infanrix hexa™ booster in the second year of life. History of or intercurrent hepatitis B disease. Hepatitis B vaccination at birth. 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 hepatitis B vaccine challenge dose. Administration of immunoglobulins and/or any blood products within the three months preceding challenge dose or planned administration during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose of HBV vaccine. History of any reaction or hypersensitivity likely to be exacerbated by any component of the hepatitis B vaccine, or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease and/or fever at the time of enrolment.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 8 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 previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life received a single dose of Engerix-B Kinder vaccine as an intramuscular (IM) injection into the deltoid region of the non-dominant arm at 7-8 years of age. | Biological: Engerix-B™ Kinder<br>* Intramuscular, single dose<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 (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) | A decrease in the specificity of the anti-HBs enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of anti-HBs antibodies (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi-Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HBs Antibody Concentrations After Previous Vaccination With Infanrix Hexa Vaccine. | Antibody concentrations are expressed as Geometric mean antibody concentrations (GMCs) in mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi-Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | Before (Day 0) a challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above the Protocol Specified Cut-off Values After Previous Vaccination With Infanrix Hexa Vaccine | Anti-HBs antibody concentrations cut-off values assessed were ≥ 6.2 mIU/mL (previously 3.3 mIU/mL), ≥ 10 mIU/mL, ≥ 10 mIU/mL to <100 mIU/mL and ≥ 100 mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi-Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. | Before (Day 0) a challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values | Anti-HBs antibody concentrations cut-off values assessed were ≥ 6.2 mIU/mL (previously 3.3 mIU/mL) and ≥ 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of anti-HBs antibodies (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi-Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. | One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine | 
| Anti-HBs Antibody Concentrations | Antibody concentrations are expressed as Geometric mean antibody concentrations (GMCs) in mIU/mL. A decrease in the specificity of the anti-HBs had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi-Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects Demonstrating an Anamnestic Response to the Engerix-B Kinder Challenge Dose | The anamnestic response is defined as an antibody concentration ≥ 10 mIU/mL at post Engerix-B Kinder challenge dose time point for initially seronegative subjects ,and as an antibody concentration at post Engerix-B Kinder challenge dose time point ≥ 4 fold the pre-vaccination antibody concentration for initially seropositive subjects. A seropositive/seronegative subject was defined as subject with HBs antibody concentration below/greater than or equal to the seropositivity cut-off of 6.2 mIU/mL. A decrease in the specificity of the anti-HBs ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. | After Engerix-B Kinder challenge dose (Month 1) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Solicited local symptoms assessed were pain, redness and swelling. Any was occurrence of any local symptom regardless of their intensity grade. Grade 3 pain was considerable pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was > 50 millimeter (mm). | During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and temeperature. Any temperature was defined as axillary temperature ≥ 37.5 degree centigrade (°C), grade 3 temperature was axillary temperature > 39.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination. | During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects Reporting Any Unsolicited 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 (Day 0-30) follow-up period after the challenge dose of Engerix-B Kinder vaccine | 
| Number of Subjects Reporting Any 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. | After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune response, Engerix-B™Kinder, Persistence, challenge dose