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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01333813
First received: April 7, 2011
Last updated: January 30, 2014
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis B
Biological: Engerix-B™ Kinder
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) [ Time Frame: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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:
  • Anti-HBs Antibody Concentrations After Previous Vaccination With Infanrix Hexa Vaccine. [ Time Frame: Before (Day 0) a challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]

    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 [ Time Frame: Before (Day 0) a challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values [ Time Frame: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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.

  • Anti-HBs Antibody Concentrations [ Time Frame: One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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 [ Time Frame: After Engerix-B Kinder challenge dose (Month 1) ] [ Designated as safety issue: No ]
    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 and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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, Grade 3 and Related Solicited General AEs [ Time Frame: During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]

    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 Reporting Any Unsolicited AEs [ Time Frame: During the 31-day (Day 0-30) follow-up period after the challenge dose of Engerix-B Kinder vaccine ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Any Serious Adverse Events (SAEs) [ Time Frame: After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1) ] [ Designated as safety issue: No ]
    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.


Enrollment: 300
Study Start Date: April 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Engerix-B Kinder Group
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
Intramuscular, single dose

  Eligibility

Ages Eligible for Study:   7 Years to 8 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01333813

Locations
Germany
GSK Investigational Site
Bad Saulgau, Baden-Wuerttemberg, Germany, 88348
GSK Investigational Site
Kehl, Baden-Wuerttemberg, Germany, 77694
GSK Investigational Site
Oberstenfeld, Baden-Wuerttemberg, Germany, 71720
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70469
GSK Investigational Site
Tuttlingen, Baden-Wuerttemberg, Germany, 78532
GSK Investigational Site
Bindlach, Bayern, Germany, 95463
GSK Investigational Site
Kempten, Bayern, Germany, 87435
GSK Investigational Site
Braunatal, Hessen, Germany, 34225
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48163
GSK Investigational Site
Frankenthal, Rheinland-Pfalz, Germany, 67227
GSK Investigational Site
Worms, Rheinland-Pfalz, Germany, 67547
GSK Investigational Site
Berlin, Germany, 13055
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01333813     History of Changes
Other Study ID Numbers: 112688
Study First Received: April 7, 2011
Results First Received: July 19, 2012
Last Updated: January 30, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by GlaxoSmithKline:
immune response
Engerix-B™Kinder
Persistence
challenge dose

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antibodies
Hepatitis B Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014