Clinical Trial Results:
An open, phase IV, single-group, multicenter study to assess the long-term persistence of antibodies against hepatitis B and the immune response to a challenge dose of Engerix™-B Kinder in adolescents 15-16 years of age who were vaccinated in infancy with three doses of Engerix™-B Kinder.
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Summary
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EudraCT number |
2012-003950-10 |
Trial protocol |
DE |
Global end of trial date |
21 Feb 2014
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Results information
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Results version number |
v3(current) |
This version publication date |
28 Mar 2023
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First version publication date |
29 May 2015
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Other versions |
v1 , v2 |
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 |
116722
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01847430 | ||
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 Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, 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 |
14 Jul 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Feb 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Feb 2014
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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 Engerix-B Kinder in subjects 15-16 years of age vaccinated with three doses of Engerix-B Kinder in infancy.
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Protection of trial subjects |
The subjects were observed closely for at least 30 minutes following the administration of the vaccine, with appropriate medical treatment readily available in case of anaphylaxis.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jul 2013
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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: 303
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Worldwide total number of subjects |
303
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EEA total number of subjects |
303
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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) |
0
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Adolescents (12-17 years) |
303
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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 |
One subject from the total number of 303 subjects enrolled did not qualify to start the study due to a protocol violation. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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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. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Engerix™-B Kinder
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Investigational medicinal product code |
SB103860
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Single dose of HBV administered intramuscularly in the deltoid region of the non-dominant arm
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One subject from the total number of 303 subjects enrolled did not qualify to start the study due to a protocol violation. |
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Baseline characteristics reporting groups
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Reporting group title |
HBV Group
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
HBV Group
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Reporting group 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. | ||
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End point title |
Number of subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut off value [1] | ||||||||
End point description |
The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
One month after the challenge dose (Month 1)
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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 scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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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 Symptoms | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) follow-up period after the challenge dose
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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 Symptoms | ||||||||||||||||||||||||||||||
End point 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
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) follow-up period after the challenge dose
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of Subjects Reporting Unsolicited Adverse Events (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 (Days 0-30) follow-up period after the challenge dose
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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 |
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.
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End point type |
Secondary
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End point timeframe |
During the entire study period (Day 0 to Month 1)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects with an anamnestic response to the challenge dose in relation to their pre-vaccination status | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Prior to vaccination with the challenge dose
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut off value | ||||||||||||||||||
End point description |
The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
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End point type |
Secondary
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End point timeframe |
Before (Day 0) and one month after the challenge dose (Month 1)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Antibody titers against hepatitis B virus | ||||||||||||
End point description |
Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs.
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End point type |
Secondary
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End point timeframe |
Before (Day 0) and one month (Month 1) after the challenge dose
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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: During the entire study period (Day 0 to Month 1), Solicited local and general symptoms: During the 4-day (Days 0-3) follow-up period after the HBV challenge dose.
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Adverse event reporting additional description |
The number of occurrences reported for solicited symptoms, adverse events, and serious adverse events were not available for posting. The number of subjects affected by each specific event was indicated as the number of occurrences.
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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 |
17
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Reporting groups
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Reporting group title |
HBV Group
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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20 Jun 2013 |
• GSK has discontinued the use of its in-house Enzyme-Linked ImmunoSorbent Assay (ELISA) that was used to measure anti-HBs (antibodies to Hepatitis B surface antigen) antibody concentrations. This assay is being replaced by ChemiLuminescence ImmunoAssay (CLIA). The new assay cut-off is 6.2 mIU/ml and is updated throughout the protocol.
• The threshold level of prednisone in this study has been modified from 0.5 mg/kg/day to 20 mg/day, in order to align the dosage with that prescribed for adolescents.
• The primary objective was not stated correctly in the sample size section. This has been amended to state that despite the primary objective being descriptive, the sample size has been computed, on the assumption that 90% antibody persistence would be observed.
• The intensity of local injection site redness/swelling has been corrected to indicate the scale reflective for adolescents and adults. Several typos in the table for the maximum intensity of fever have also been rectified in the same section.
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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 | |||
