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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 31, 2014