Clinical Trial Results:
An open, phase IV, multicentre study to assess the long-term persistence of antibodies against hepatitis B and the immune response to a hepatitis B (Engerix-B™ Kinder) vaccine challenge in children aged 7–8 years, previously primed and boosted in the first two years of life with GlaxoSmithKline (GSK) Biologicals’ DTPa-HBV-IPV/Hib (Infanrix hexa™) vaccine
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Summary
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EudraCT number |
2010-022538-10 |
Trial protocol |
DE |
Global end of trial date |
28 Sep 2011
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Results information
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Results version number |
v2(current) |
This version publication date |
14 May 2018
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First version publication date |
20 Feb 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
112688
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01333813 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Sep 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Sep 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
•To assess the anti-HBs antibody response to a challenge dose of HBV vaccine (Engerix-B Kinder) in subjects 7–8 years of age, previously vaccinated with four doses of Infanrix hexa in the first two years of life.
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Protection of trial subjects |
In order to ensure proper IM injection of the study vaccine, a needle of at least 1 inch (2.54 cm) length, 25 gauge was used.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Apr 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 297
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Worldwide total number of subjects |
297
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EEA total number of subjects |
297
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
297
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
A total of 300 subjects were enrolled in the study. Among them 297 subjects were included in the Total Vaccinated cohort. Remaining 3 subjects were not included as they failed to meet protocol specified criteria and as such they are not included in the Participant Flow as Started. | ||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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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. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Engerix-B™ Kinder
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Intramuscular, single dose.
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Baseline characteristics reporting groups
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Reporting group title |
Engerix-B Kinder Group
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Reporting group description |
Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Engerix-B Kinder Group
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Reporting group description |
Subjects previously primed and boosted with 4 doses of Infanrix hexa vaccine in the first 2 years of life. | ||
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End point title |
Number of subjects with anti-hepatitis B (anti-HBs) antibody concentration equal to or above (≥) 100 milli-International units per milliliter (mIU/mL) [1] | ||||||||
End point 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.
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End point type |
Primary
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End point timeframe |
Number of subjects with anti-hepatitis B (anti-HBs) antibody concentration equal to or above (≥) 100 milli-International units per milliliter (mIU/mL)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Anti-HBs antibody concentrations after previous vaccination with Infanrix hexa vaccine. | ||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Before (Day 0) a challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||||
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End point 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 | ||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Before (Day 0) a challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of subjects with anti-HBs antibody concentrations equal to or above protocol specified cut-off values | ||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||||
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End point title |
Anti-HBs antibody concentrations | ||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
One month (Month 1) after a challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of subjects demonstrating an anamnestic response to the Engerix-B Kinder challenge dose | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
After Engerix-B Kinder challenge dose (Month 1)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects reporting any and grade 3 solicited local Adverse Events (AEs) | ||||||||||||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Number of subjects reporting any and grade 3 solicited local Adverse Events (AEs)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of subjects reporting any, grade 3 and related solicited general AEs | ||||||||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 0-3) follow-up period after the challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of subjects reporting any unsolicited AEs | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
During the 31-day (Day 0-30) follow-up period after the challenge dose of Engerix-B Kinder vaccine
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects reporting any serious adverse events (SAEs) | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
After the challenge dose of Engerix-B Kinder vaccine up to the study end (Day 0 to Month 1)
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events were assessed from Day 0 to Month 1. Systematically assessed frequent adverse events were assessed during the 4-day post vaccination period.
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Adverse event reporting additional description |
The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.0
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Reporting groups
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Reporting group title |
Engerix-B Kinder Group
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
