Back to resultsHepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children
Primary Purpose
Hepatitis B
Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Engerix-B™ Kinder
Sponsored by
About this trial
This is an interventional prevention trial for Hepatitis B focused on measuring immune response, Engerix-B™Kinder, Persistence, challenge dose
Eligibility 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.
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
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Engerix-B Kinder Group
Arm Description
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.
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-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.
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
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
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
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
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)
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
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
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01333813
Brief Title
Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 26, 2011 (undefined)
Primary Completion Date
September 28, 2011 (Actual)
Study Completion Date
September 28, 2011 (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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
immune response, Engerix-B™Kinder, Persistence, challenge dose
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Engerix-B Kinder Group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Engerix-B™ Kinder
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-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.
Time Frame
One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
Secondary Outcome Measure Information:
Title
Anti-HBs Antibody Concentrations After Previous Vaccination With Infanrix Hexa Vaccine.
Description
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.
Time Frame
Before (Day 0) a challenge dose of Engerix-B Kinder vaccine
Title
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
Description
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.
Time Frame
Before (Day 0) a challenge dose of Engerix-B Kinder vaccine
Title
Number of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Protocol Specified Cut-off Values
Description
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.
Time Frame
One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
Title
Anti-HBs Antibody Concentrations
Description
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.
Time Frame
One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
Title
Number of Subjects Demonstrating an Anamnestic Response to the Engerix-B Kinder Challenge Dose
Description
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.
Time Frame
After Engerix-B Kinder challenge dose (Month 1)
Title
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)
Description
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).
Time Frame
During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine
Title
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs
Description
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.
Time Frame
During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine
Title
Number of Subjects Reporting Any Unsolicited AEs
Description
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.
Time Frame
During the 31-day (Day 0-30) follow-up period after the challenge dose of Engerix-B Kinder vaccine
Title
Number of Subjects Reporting Any Serious Adverse Events (SAEs)
Description
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.
Time Frame
After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
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
Bad Saulgau
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
88348
Country
Germany
Facility Name
GSK Investigational Site
City
Kehl
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
77694
Country
Germany
Facility Name
GSK Investigational Site
City
Oberstenfeld
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
71720
Country
Germany
Facility Name
GSK Investigational Site
City
Stuttgart
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
70469
Country
Germany
Facility Name
GSK Investigational Site
City
Tuttlingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
78532
Country
Germany
Facility Name
GSK Investigational Site
City
Bindlach
State/Province
Bayern
ZIP/Postal Code
95463
Country
Germany
Facility Name
GSK Investigational Site
City
Kempten
State/Province
Bayern
ZIP/Postal Code
87435
Country
Germany
Facility Name
GSK Investigational Site
City
Braunatal
State/Province
Hessen
ZIP/Postal Code
34225
Country
Germany
Facility Name
GSK Investigational Site
City
Muenster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48163
Country
Germany
Facility Name
GSK Investigational Site
City
Frankenthal
State/Province
Rheinland-Pfalz
ZIP/Postal Code
67227
Country
Germany
Facility Name
GSK Investigational Site
City
Worms
State/Province
Rheinland-Pfalz
ZIP/Postal Code
67547
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13055
Country
Germany
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.
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
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112688
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
112688
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
112688
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
112688
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
112688
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112688
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Hepatitis B Antibody Persistence and Immune Response to Hepatitis B Vaccine Challenge in Previously Vaccinated Children
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