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

Primary Purpose

Hepatitis B

Status
Completed
Phase
Phase 4
Locations
Slovakia
Study Type
Interventional
Intervention
Engerix™-B
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatitis B focused on measuring Persistence, challenge dose, Engerix-B, immune response

Eligibility Criteria

11 Years - 12 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Infanrix-hexa/Engerix-B Group

Infanrix-IPV+Hib/Engerix-B Group

Arm Description

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.

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.

Outcomes

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)
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
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
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
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
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
Solicited local symptoms assessed were pain, redness and swelling.
Number of Subjects Reporting Solicited General Symptoms
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)
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)
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.

Full Information

First Posted
May 27, 2010
Last Updated
July 19, 2018
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01138098
Brief Title
Evaluation of Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in Previously Vaccinated Children
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
June 7, 2010 (undefined)
Primary Completion Date
November 26, 2010 (Actual)
Study Completion Date
November 26, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Persistence, challenge dose, Engerix-B, immune response

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
185 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Infanrix-hexa/Engerix-B Group
Arm Type
Experimental
Arm Description
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.
Arm Title
Infanrix-IPV+Hib/Engerix-B Group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Engerix™-B
Intervention Description
Intramuscular, single dose
Primary Outcome Measure Information:
Title
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)
Description
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.
Time Frame
One month after a challenge dose of Engerix-B vaccine
Secondary Outcome Measure Information:
Title
Number of Subjects With an Anamnestic Response to a Challenge Dose
Description
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.
Time Frame
Before and one month after a challenge dose of Engerix-B vaccine
Title
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
Description
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.
Time Frame
Before and one month after a challenge dose of Engerix-B vaccine
Title
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
Description
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.
Time Frame
Before and one month after a challenge dose of Engerix-B vaccine
Title
Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL
Description
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.
Time Frame
Before the challenge dose of Engerix-B vaccine
Title
Number of Subjects Reporting Solicited Local Symptoms
Description
Solicited local symptoms assessed were pain, redness and swelling.
Time Frame
During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Title
Number of Subjects Reporting Solicited General Symptoms
Description
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)).
Time Frame
During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Title
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine
Title
Number of Subjects Reporting Serious Adverse Events (SAEs)
Description
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.
Time Frame
After the challenge dose of Engerix-B vaccine up to the study end

10. Eligibility

Sex
All
Minimum Age & Unit of Time
11 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Banska Bystrica
ZIP/Postal Code
974 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Dolny Kubin
ZIP/Postal Code
026 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Dubnica Nad Vahom
ZIP/Postal Code
018 41
Country
Slovakia
Facility Name
GSK Investigational Site
City
Martin
ZIP/Postal Code
036 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Nitra
ZIP/Postal Code
949 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Nova Dubnica
ZIP/Postal Code
018 51
Country
Slovakia
Facility Name
GSK Investigational Site
City
Nove Zamky
ZIP/Postal Code
940 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Puchov
ZIP/Postal Code
020 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Roznava
ZIP/Postal Code
048 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Trebisov
ZIP/Postal Code
075 01
Country
Slovakia
Facility Name
GSK Investigational Site
City
Zlate Moravce
ZIP/Postal Code
953 01
Country
Slovakia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
24962750
Citation
Avdicova M, Crasta PD, Hardt K, Kovac M. Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age. Vaccine. 2015 May 28;33(23):2727-33. doi: 10.1016/j.vaccine.2014.06.070. Epub 2014 Jun 22.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113954
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

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