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Evaluation of Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in Previously Vaccinated Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01138098
First received: May 27, 2010
Last updated: January 23, 2014
Last verified: January 2012
  Purpose

This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in 11-12 Year Old Children, Previously Vaccinated With DTPa-HBV-IPV/Hib Vaccine in Study 217744/031

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 after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (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.


Secondary Outcome Measures:
  • Number of Subjects With an Anamnestic Response to a Challenge Dose [ Time Frame: Before and one month after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB 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 With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL [ Time Frame: Before and one month after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB 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 With Anti-HBs Antibody Concentration ≥ 10 mIU/mL [ Time Frame: Before and one month after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (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.

  • Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL [ Time Frame: Before the challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB 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.

  • Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling.

  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)).

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix™-B vaccine ] [ Designated as safety issue: No ]
    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: After the challenge dose of Engerix™-B vaccine up to the study end ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.


Enrollment: 185
Study Start Date: June 2010
Study Completion Date: November 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Infanrix-hexa/Engerix-B Group
Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Biological: Engerix™-B
Intramuscular, single dose
Active Comparator: Infanrix-IPV+Hib/Engerix-B Group
Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm.
Biological: Engerix™-B
Intramuscular, single dose

Detailed Description:

Subjects who participated in the primary study 217744/031 (NCT01457495) will be invited at the age of 11-12 years to participate in this follow-up study.

  Eligibility

Ages Eligible for Study:   11 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parents/Legally acceptable representative) can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female aged 11-12 years at the time of study entry (from and including the 11th birthday until and excluding the 13th birthday).
  • Written informed consent obtained from the parent or Legally Acceptable Representative of the subject.
  • Study procedures will be explained to subjects and depending on their understanding, optional informed assent will be sought at the discretion of the investigator.
  • Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative (s).
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Subjects who have received all three doses of Infanrix hexa or Engerix-B in the primary study 217744/031 (NCT01457495).
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • 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:

  • 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.
  • Child in care.
  • Use of any investigational or non-registered product drug or vaccine) other than the study vaccine within 30 days preceding the challenge dose of HBV vaccine, or planned use during the study period.
  • Receipt of hepatitis B (containing) vaccine after vaccination in the primary study 217744/031 (NCT01457495).
  • History of hepatitis B disease.
  • 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 vaccine challenge dose.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the challenge dose of HBV vaccine 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.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
  • Known hypersensitivity to any component of the HBV vaccine or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component.
  • Acute disease and/or fever at the time of enrolment.
  • Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting
  • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  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: NCT01138098

Locations
Slovakia
GSK Investigational Site
Banska Bystrica, Slovakia, 974 01
GSK Investigational Site
Dolny Kubin, Slovakia, 026 01
GSK Investigational Site
Dubnica Nad Vahom, Slovakia, 018 41
GSK Investigational Site
Martin, Slovakia, 036 01
GSK Investigational Site
Nitra, Slovakia, 949 01
GSK Investigational Site
Nova Dubnica, Slovakia, 018 51
GSK Investigational Site
Nove Zamky, Slovakia, 940 01
GSK Investigational Site
Puchov, Slovakia, 020 01
GSK Investigational Site
Roznava, Slovakia, 048 01
GSK Investigational Site
Trebisov, Slovakia, 075 01
GSK Investigational Site
Zlate Moravce, Slovakia, 953 01
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Avdicova M et al. Lasting immune memory against Hepatitis B in 11-12 year old children previously vaccinated with 2+1 doses of DTPa-HBV-IPV/HIB or DTPa-IPV/Hib+HBV. Abstract presented at the 30th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), Thessaloniki, Greece, 8-12 May 2012.

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01138098     History of Changes
Other Study ID Numbers: 113954
Study First Received: May 27, 2010
Results First Received: November 10, 2011
Last Updated: January 23, 2014
Health Authority: Slovakia: State Institute for Drug Control

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

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014