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Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder

Primary Purpose

Hepatitis B

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Engerix™-B Kinder
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 Healthy, Hepatitis B, Adolescents, Engerix™-B Kinder

Eligibility Criteria

15 Years - 16 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Subject's parent(s)/guardians who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
  • A male or female between, and including, 15 and 16 years of age at the time of the vaccination.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject.
  • Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/LAR(s).
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Documented evidence of previous vaccination with three consecutive doses of Engerix™-B Kinder in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age.

  • Female subjects of non-childbearing potential may be enrolled in the study.

    • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

  • 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.

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.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
  • Previous hepatitis B vaccination since administration of the third dose of Engerix™-B Kinder.
  • History of hepatitis B disease.
  • Administration of a vaccine not foreseen by the study protocol within the period starting 30 days before study vaccine dose, or planned administration 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 vaccine/product.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

  • Acute disease and/or fever at the time of enrollment.

    • Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary.
    • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the study vaccine dose or planned administration during the study period.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HBV Group

Arm Description

Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.

Outcomes

Primary Outcome Measures

Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.
The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).

Secondary Outcome Measures

Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.
The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
Antibody Titers Against Hepatitis B Virus
Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs.
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status.
Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to ) 4-fold rise in post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. >50 mm.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C
Number of Subjects Reporting Unsolicited Adverse Events (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).
Serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was 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

First Posted
May 2, 2013
Last Updated
July 2, 2018
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01847430
Brief Title
Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder
Official Title
Long-term Persistence of Hepatitis B Antibodies and Immune Response to a Challenge Dose of GSK Biologicals' Hepatitis B Virus Vaccine, Engerix™-B Kinder (SKF103860), in 15-16 Years Old Adolescents, Vaccinated in Infancy With Engerix™-B Kinder
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
July 19, 2013 (undefined)
Primary Completion Date
February 21, 2014 (Actual)
Study Completion Date
February 21, 2014 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to assess the long-term persistence of immunity to hepatitis B in adolescents aged 15-16 years who were vaccinated with Engerix™-B Kinder in infancy. The study will also assess the immune response to a challenge dose of Engerix™-B Kinder in these subjects.
Detailed Description
This MDD has been updated following the Protocol Amendment 1, dated 20 June 2013. The Protocol was amended because GSK replaced its in-house Enzyme-Linked ImmunoSorbent Assay (ELISA) that was used to measure anti-HBs (antibodies to Hepatitis B surface antigen) antibody concentrations with ChemiLuminescence ImmunoAssay (CLIA). Additionally, the threshold level of prednisone was modified to reflect the dosage normally prescribed to adolescents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Healthy, Hepatitis B, Adolescents, Engerix™-B Kinder

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
303 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HBV Group
Arm Type
Experimental
Arm Description
Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Intervention Type
Biological
Intervention Name(s)
Engerix™-B Kinder
Intervention Description
Single dose administered intramuscularly in the deltoid region of non-dominant arm at Day 0.
Primary Outcome Measure Information:
Title
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.
Description
The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).
Time Frame
One month after the challenge dose (Month 1)
Secondary Outcome Measure Information:
Title
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.
Description
The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
Time Frame
Before (Day 0) and one month after the challenge dose (Month 1)
Title
Antibody Titers Against Hepatitis B Virus
Description
Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs.
Time Frame
Before (Day 0) and one month (Month 1) after the challenge dose
Title
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status.
Description
Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to ) 4-fold rise in post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point
Time Frame
Prior to vaccination with the challenge dose
Title
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Description
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. >50 mm.
Time Frame
During the 4-day (Days 0-3) follow-up period after the challenge dose
Title
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Description
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C
Time Frame
During the 4-day (Days 0-3) follow-up period after the challenge dose
Title
Number of Subjects Reporting Unsolicited Adverse Events (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 (Days 0-30) follow-up period after the challenge dose
Title
Number of Subjects Reporting Any Serious Adverse Events (SAEs).
Description
Serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was 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
During the entire study period (Day 0 to Month 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subject's parent(s)/guardians who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. A male or female between, and including, 15 and 16 years of age at the time of the vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/LAR(s). Healthy subjects as established by medical history and clinical examination before entering into the study. Documented evidence of previous vaccination with three consecutive doses of Engerix™-B Kinder in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. 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. 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. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Previous hepatitis B vaccination since administration of the third dose of Engerix™-B Kinder. History of hepatitis B disease. Administration of a vaccine not foreseen by the study protocol within the period starting 30 days before study vaccine dose, or planned administration 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 vaccine/product. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease and/or fever at the time of enrollment. Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the 3 months preceding the study vaccine dose or planned administration during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.
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
Kehl
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
77694
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
Kirchheim
State/Province
Bayern
ZIP/Postal Code
85551
Country
Germany
Facility Name
GSK Investigational Site
City
Goch
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
47574
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
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04178
Country
Germany
Facility Name
GSK Investigational Site
City
Flensburg
State/Province
Schleswig-Holstein
ZIP/Postal Code
24937
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13055
Country
Germany
Facility Name
GSK Investigational Site
City
Neumuenster
ZIP/Postal Code
24534
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://clinicalstudydatarequest.com
Citations:
PubMed Identifier
27095043
Citation
Van Der Meeren O, Behre U, Crasta P. Immunity to hepatitis B persists in adolescents 15-16 years of age vaccinated in infancy with three doses of hepatitis B vaccine. Vaccine. 2016 May 23;34(24):2745-9. doi: 10.1016/j.vaccine.2016.04.013. Epub 2016 Apr 16.
Results Reference
derived
Links:
URL
https://clinicalstudydatarequest.com
Description
IPD for this study will be made available via the Clinical Study Data Request site.

Learn more about this trial

Evaluation of the Long-term Persistence of Immunity to Hepatitis B, in Adolescents Vaccinated in Infancy With Engerix™-B Kinder

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