Clinical Trial Results:
A phase IV, open, multicentric study to evaluate the immune response to a hepatitis B challenge dose in healthy subjects, 72 to 78 months after they received a primary vaccination course of GSK Biologicals’ Engerix™-B (thiomersal-free 20 µg or preservative-free 10 µg) vaccine, in the primary study HBV-280.
Summary
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EudraCT number |
2007-000261-38 |
Trial protocol |
BE |
Global end of trial date |
14 May 2008
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Results information
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Results version number |
v1 |
This version publication date |
13 May 2016
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First version publication date |
04 Dec 2014
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Other versions |
v2 |
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 |
108988
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00524576 | ||
WHO universal trial number (UTN) |
- | ||
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 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 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 May 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 May 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
14 May 2008
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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 immune response to a challenge dose of hepatitis B vaccine administered in subjects who previously received a complete hepatitis B primary vaccination course, 72 to 78 months ago.
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Protection of trial subjects |
As with all injectable vaccines, appropriate medical treatment was always readily available in case of anaphylactic reactions following the administration of the vaccine.
For this reason, the subjects remained under medical supervision for 30 minutes after vaccination.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Nov 2007
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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 |
Australia: 67
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Country: Number of subjects enrolled |
Belgium: 77
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Worldwide total number of subjects |
144
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EEA total number of subjects |
77
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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) |
72
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Adults (18-64 years) |
72
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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 |
- | |||||||||
Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. | |||||||||
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 |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Engerix 2 doses + challenge dose | |||||||||
Arm description |
Subjects received 2 doses of Engerix™-B (Month 0 and 6) and a placebo at Month 1 in the primary study and a single dose of Engerix™-B during the booster study. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Biological: Engerix™-B
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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 |
Subjects received 2 doses of Engerix™-B (Month 0 and 6) and a placebo at Month 1 in the primary study and a single dose of Engerix™-B during the booster study.
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Arm title
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Engerix 3 doses + challenge dose | |||||||||
Arm description |
Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Engerix™-B
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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 |
Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study.
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Baseline characteristics reporting groups
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Reporting group title |
Engerix 2 doses + challenge dose
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Reporting group description |
Subjects received 2 doses of Engerix™-B (Month 0 and 6) and a placebo at Month 1 in the primary study and a single dose of Engerix™-B during the booster study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Engerix 3 doses + challenge dose
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Reporting group description |
Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Engerix 2 doses + challenge dose
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Reporting group description |
Subjects received 2 doses of Engerix™-B (Month 0 and 6) and a placebo at Month 1 in the primary study and a single dose of Engerix™-B during the booster study. | ||
Reporting group title |
Engerix 3 doses + challenge dose
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Reporting group description |
Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study. |
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End point title |
Number of participants with immunological response to challenge dose in terms of anti-hepatitis B surface antigen (anti-HBs) antibody concentration [1] | ||||||||||||
End point description |
Immune response defined as: *For initially seronegative subjects (anti-HBs antibody concentration <3.3 milli-international unit per milliliter [mIU/mL] before vaccination) antibody concentration ≥ 10mIU/mL at post booster. *For initially seropositive subjects: antibody concentration at post booster ≥ 4-fold the pre-vaccination antibody concentration.
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End point type |
Primary
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End point timeframe |
30 days post-challenge dose
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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 |
Number of participants with anti-HBs antibody concentrations above the cut-off value | ||||||||||||||||||
End point description |
Anti-HBs antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL.
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End point type |
Secondary
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End point timeframe |
30 days post-challenge dose
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No statistical analyses for this end point |
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End point title |
Concentration of anti-HBs antibodies | |||||||||||||||
End point description |
Concentrations given as geometric mean concentration (GMC) and expressed in mIU/mL.
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End point type |
Secondary
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End point timeframe |
30 days post-challenge dose
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No statistical analyses for this end point |
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End point title |
Number of participants reporting solicited local symptoms | ||||||||||||||||||
End point description |
Solicited local symptoms assessed include pain, redness and swelling.
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End point type |
Secondary
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End point timeframe |
During the 4-day follow-up period (Day 0-3) after the challenge dose
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No statistical analyses for this end point |
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End point title |
Number of participants reporting solicited general symptoms | |||||||||||||||||||||
End point description |
Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms, and headache.
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End point type |
Secondary
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End point timeframe |
During the 4-day follow-up period (Day 0-3) after the challenge dose
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No statistical analyses for this end point |
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End point title |
Number of participants reporting unsolicited adverse events (AE) | ||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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End point type |
Secondary
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End point timeframe |
During the 31-day follow-up period (Day 0-30) after the challenge dose
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No statistical analyses for this end point |
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End point title |
Number of participants reporting serious adverse events (SAE) | ||||||||||||
End point description |
An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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End point type |
Secondary
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End point timeframe |
During the 31-day follow-up period (Day 0-30) 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 (SAE) = Day 0 to Day 30. Solicited local and general symptoms =During the 4-day (Days 0-3) post-challenge dose period. Unsolicited AEs = during the 31-day (Day 0-30) follow-up period after the HBV challenge dose.
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Adverse event reporting additional description |
For the other adverse events: Data from the Australian center were not included following data quality issues detected at the investigator site.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Engerix 2 doses + challenge dose
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Reporting group description |
Subjects received 2 doses of Engerix™-B (Month 0 and 6) and a placebo at Month 1 in the primary study and a single dose of Engerix™-B during the booster study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Engerix 3 doses + challenge dose
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Reporting group description |
Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to the adverse event may differ from the total number of subjects exposed for the reporting group as for the unsolicited adverse events, not all subjects reported an event and hence, were considered as subjects without an event. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: For the solicited local and general symptoms, not all subjects had their symptom sheets completed therefore, the analysis of the solicited symptoms based on the Total Vaccinated cohort included only subjects with documented safety data (i.e. symptom sheet completed). |
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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 |