Back to resultsLT F-up Study 16-20 Yrs After Vaccine Dose of Hepatitis B With/Without HBIg in Newborns to HBeAg+ Mothers
Primary Purpose
Hepatitis B
Status
Completed
Phase
Phase 4
Locations
Thailand
Study Type
Interventional
Intervention
Engerix™ -B
Hepatitis B immunoglobulin (HBIg)
Sponsored by
About this trial
This is an interventional prevention trial for Hepatitis B focused on measuring Hepatitis B immunoglobulin, Hepatitis B antibody persistence
Eligibility Criteria
Inclusion Criteria: Subjects who had received at least one dose of the study vaccine in the primary study Written informed consent obtained from each subject before each blood sampling visit Exclusion Criteria: None
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Engerix 4D + HBIg Group
Engerix 3D + HBIg Group
Engerix 4D
Engerix 3D Group
Arm Description
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm.
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm.
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60.
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6.
Outcomes
Primary Outcome Measures
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
Note: At Year 15 and 16, a commercial ELISA was used. From Year 17 to Year 20, anti-HBs antibody concentrations were tested with a validated in-house assay with cut-off 3.3mIU/mL.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ChemiLuminescence ImmunoAssay (CLIA).
Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
Note: There was a change of assay kit at Year 19 time-point, thus for the sake of bridging, blood samples corresponding to Year 19 were re-tested with new CLIA. At Year 19 and 20, anti-HBs antibody concentrations tested with the CLIA with cut-off 6.2 mIU/mL.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values Enzyme-Linked Immunosorbent Assay (ELISA).
Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL.
Adjusted Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values as Measured by ChemiLuminescence ImmunoAssay (CLIA)
Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL.
Note: Missing CLIA anti-HBs concentrations, for subjects with ELISA results available, are estimated by multiple imputations and GMCs and number of subjects were adjusted for these imputations.
Number of Subjects With Positive Results for Serological Markers for Hepatitis B Infection
Serological markers for hepatitis B infection assessed are hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg) and antibodies to hepatitis B e antigen (anti-HBe).
Number of Subjects With Different Hepatitis B Infection Statuses
Categories hepatitis B (HB) infection:
Chronic infection: HBsAg and anti-HBc pos (pos) in more than two consecutive samples
False positive: single HB marker (HBsAg, HBeAg, anti-HBc) pos + all other markers negative (neg) in one sample. Consecutive time points all neg.
Possible subclinical breakthrough infection: One or more HB markers pos in one or more consecutive samples.
Isolated natural booster: >4-fold increase of anti-HBs concentrations if <100 mIU/mL at previous sample OR >2- fold increase of anti-HBs concentrations if >=100 mIU/mL at previous sample + other markers neg
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00240526
Brief Title
LT F-up Study 16-20 Yrs After Vaccine Dose of Hepatitis B With/Without HBIg in Newborns to HBeAg+ Mothers
Official Title
Comparative Study of the Immunogenicity and Protective Efficacy of GlaxoSmithKline Biologicals' Rec-DNA Hepatitis B Vaccine With or Without Hepatitis B Immunoglobulins (HBIg) in Newborns of HBeAg+ Mothers.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
To evaluate the persistence of anti-HBs antibodies up to 16, 17, 18, 19 and 20 years after administration of the first dose of the study vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.
Detailed Description
The primary study was to evaluate the reactogenicity, immunogenicity and protective efficacy of a hepatitis B vaccine in healthy neonates of HBeAg positive mothers if administered with or without a dose of HBIg at birth. The current study describes the long term follow up of these subjects between Y16 and 20 after primary vaccination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Hepatitis B immunoglobulin, Hepatitis B antibody persistence
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
79 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Engerix 4D + HBIg Group
Arm Type
Experimental
Arm Description
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm.
Arm Title
Engerix 3D + HBIg Group
Arm Type
Experimental
Arm Description
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm.
Arm Title
Engerix 4D
Arm Type
Experimental
Arm Description
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60.
Arm Title
Engerix 3D Group
Arm Type
Experimental
Arm Description
Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6.
Intervention Type
Biological
Intervention Name(s)
Engerix™ -B
Intervention Description
3 (Groups A and C) or 4 (Groups B and D) intramuscular injections during the primary study
Intervention Type
Biological
Intervention Name(s)
Hepatitis B immunoglobulin (HBIg)
Intervention Description
1 intramuscular injections at birth (primary study)
Primary Outcome Measure Information:
Title
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Description
Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
Note: At Year 15 and 16, a commercial ELISA was used. From Year 17 to Year 20, anti-HBs antibody concentrations were tested with a validated in-house assay with cut-off 3.3mIU/mL.
Time Frame
At Years 15, 16, 17, 18, 19 and 20
Title
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ChemiLuminescence ImmunoAssay (CLIA).
Description
Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL).
Note: There was a change of assay kit at Year 19 time-point, thus for the sake of bridging, blood samples corresponding to Year 19 were re-tested with new CLIA. At Year 19 and 20, anti-HBs antibody concentrations tested with the CLIA with cut-off 6.2 mIU/mL.
Time Frame
At Years 19 and 20
Title
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values Enzyme-Linked Immunosorbent Assay (ELISA).
Description
Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL.
Time Frame
At Years 15, 16, 17, 18, 19 and 20
Title
Adjusted Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values as Measured by ChemiLuminescence ImmunoAssay (CLIA)
Description
Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL.
Note: Missing CLIA anti-HBs concentrations, for subjects with ELISA results available, are estimated by multiple imputations and GMCs and number of subjects were adjusted for these imputations.
Time Frame
At Years 19 and 20
Title
Number of Subjects With Positive Results for Serological Markers for Hepatitis B Infection
Description
Serological markers for hepatitis B infection assessed are hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg) and antibodies to hepatitis B e antigen (anti-HBe).
Time Frame
At Years 15, 16, 17, 18, 19 and 20
Title
Number of Subjects With Different Hepatitis B Infection Statuses
Description
Categories hepatitis B (HB) infection:
Chronic infection: HBsAg and anti-HBc pos (pos) in more than two consecutive samples
False positive: single HB marker (HBsAg, HBeAg, anti-HBc) pos + all other markers negative (neg) in one sample. Consecutive time points all neg.
Possible subclinical breakthrough infection: One or more HB markers pos in one or more consecutive samples.
Isolated natural booster: >4-fold increase of anti-HBs concentrations if <100 mIU/mL at previous sample OR >2- fold increase of anti-HBs concentrations if >=100 mIU/mL at previous sample + other markers neg
Time Frame
Over the entire follow up period (Final assessment of clinical significance was analyzed after the Year 20 time point)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects who had received at least one dose of the study vaccine in the primary study
Written informed consent obtained from each subject before each blood sampling visit
Exclusion Criteria:
None
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
Bangkok
ZIP/Postal Code
10330
Country
Thailand
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
22777097
Citation
Poovorawan Y, Chongsrisawat V, Theamboonlers A, Leroux-Roels G, Crasta PD, Hardt K. Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum Vaccin Immunother. 2012 Jul;8(7):896-904. doi: 10.4161/hv.19989. Epub 2012 Jul 1.
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
100450
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
100450
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
100450
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
100450
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
100450
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
100450
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
LT F-up Study 16-20 Yrs After Vaccine Dose of Hepatitis B With/Without HBIg in Newborns to HBeAg+ Mothers
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