Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children
- Conditions
- Hepatitis B
- Interventions
- Biological: Engerix-B™ Kinder
- Registration Number
- NCT01333813
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Engerix-B Kinder Group Engerix-B™ Kinder 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.
- Primary Outcome Measures
Name Time Method Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects Reporting Any Unsolicited AEs During the 31-day (Day 0-30) follow-up period after the challenge dose of Engerix-B Kinder vaccine 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.
Anti-HBs Antibody Concentrations After Previous Vaccination With Infanrix Hexa Vaccine. Before (Day 0) a challenge dose of Engerix-B Kinder 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.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 Before (Day 0) a challenge dose of Engerix-B Kinder 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.
Anti-HBs Antibody Concentrations One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine 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.
Number of Subjects Demonstrating an Anamnestic Response to the Engerix-B Kinder Challenge Dose After Engerix-B Kinder challenge dose (Month 1) 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.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine 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.Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine 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.
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine 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).
Number of Subjects Reporting Any Serious Adverse Events (SAEs) After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1) 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇩🇪Berlin, Germany