Clinical Trial Results:
An open, single centre study to evaluate the long-term antibody persistence and immune memory between 16 and 20 years after the primary study HAB-028 (208127/021) in which healthy adults were vaccinated with Twinrix™ Adult following a three-dose schedule.
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Summary
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EudraCT number |
2009-014275-53 |
Trial protocol |
BE |
Global end of trial date |
25 Jul 2014
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Results information
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Results version number |
v1 |
This version publication date |
01 Apr 2016
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First version publication date |
07 Aug 2015
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Other versions |
v2 , v3 |
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 |
112267
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01000324 | ||
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? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
01 Oct 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Mar 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jul 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 evaluate anti-HAV and anti-HBs antibody persistence at Years 16, 17, 18, 19 and 20 after a three-dose primary vaccination course with Twinrix Adult.
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Protection of trial subjects |
The subjects were observed closely for at least 30 minutes, with appropriate medical treatment readily available in case of anaphylaxis following the administration of the vaccine.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Nov 2009
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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 |
Belgium: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
0
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Adults (18-64 years) |
40
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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 |
Subjects who entered the study at Year 16, Year 17, 18 and Year 19 time points were subjects who completed the primary study and who returned for blood sampling at the considered time point. | ||||||
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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. | ||||||
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Period 1
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Period 1 title |
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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Twinrix Group | ||||||
Arm description |
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Engerix™-B
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Investigational medicinal product code |
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Other name |
HBV
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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 |
Engerix-B was administered to subjects who are not seroprotected against hepatitis B.
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Investigational medicinal product name |
Havrix™
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Investigational medicinal product code |
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Other name |
HAV
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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 |
Havrix was administered to subjects who are seronegative for anti-HAV antibodies.
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Baseline characteristics reporting groups
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Reporting group title |
Twinrix Group
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Reporting group description |
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Twinrix Group
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Reporting group description |
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | ||
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End point title |
Number of subjects with anti-hepatitis A (anti-HAV) antibody concentration equal to or above 15 milli-international units per milliliter (mIU/mL) [1] | ||||||||
End point description |
The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study
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End point type |
Primary
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End point timeframe |
At Year 16
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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 subjects with anti-hepatitis A (anti-HAV) antibody concentration equal to or above 15 milli-international units per milliliter (mIU/mL) [2] | ||||||||
End point description |
The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study
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End point type |
Primary
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End point timeframe |
At Year 17
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| Notes [2] - 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 subjects with anti-hepatitis A (anti-HAV) antibody concentration equal to or above 15 milli-international units per milliliter (mIU/mL) [3] | ||||||||
End point description |
The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study
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End point type |
Primary
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End point timeframe |
At Year 18
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| Notes [3] - 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 subjects with anti-hepatitis A (anti-HAV) antibody concentration equal to or above 15 milli-international units per milliliter (mIU/mL) [4] | ||||||||
End point description |
The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study
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End point type |
Primary
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End point timeframe |
At Year 19
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| Notes [4] - 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 |
Concentration of anti-hepatitis A (anti-HAV) antibodies [5] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 17
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| Notes [5] - 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 |
Concentration of anti-hepatitis A (anti-HAV) antibodies [6] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 18
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| Notes [6] - 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 |
Concentration of anti-hepatitis A (anti-HAV) antibodies [7] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 19
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| Notes [7] - 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 subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut-off values [8] | ||||||||||
End point description |
Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
At Year 16
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| Notes [8] - 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 subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut-off values [9] | ||||||||||
End point description |
Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
At Year 17
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| Notes [9] - 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 subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut-off values [10] | ||||||||||
End point description |
Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
At Year 18
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| Notes [10] - 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 subjects with anti-hepatitis B surface antigen (anti-HBs) antibody concentrations equal to or above the cut-off values [11] | ||||||||||
End point description |
Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).
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End point type |
Primary
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End point timeframe |
At Year 19
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| Notes [11] - 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 |
Concentration of anti-hepatitis B surface antigen (anti-HBs) antibodies [12] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 16
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| Notes [12] - 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 |
Concentration of anti-hepatitis B surface antigen (anti-HBs) antibodies [13] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 17
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| Notes [13] - 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 |
Concentration of anti-hepatitis B surface antigen (anti-HBs) antibodies [14] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 18
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| Notes [14] - 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 |
Concentration of anti-hepatitis B surface antigen (anti-HBs) antibodies [15] | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Primary
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End point timeframe |
At Year 19
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| Notes [15] - 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 |
Concentration of anti-hepatitis A (anti-HAV) antibodies | ||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs).
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End point type |
Secondary
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End point timeframe |
At Year 16
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects with immune response to the challenge vaccine antigen | ||||||||
End point description |
None of the subjects received a challenge dose at Years 16, 17 and 18 while, one subject received the challenge dose at Year 19.
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End point type |
Secondary
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End point timeframe |
Before, 14 days and one month after the challenge dose at Year 19.
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| No statistical analyses for this end point | |||||||||
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End point title |
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration | ||||||||||||||
End point description |
Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
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End point type |
Secondary
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End point timeframe |
At Year 18, 14 days and 30 days post challenge dose (Year 19)
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| Notes [16] - One subject received the challenge dose at Year 19. |
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| No statistical analyses for this end point | |||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
SAEs: during the 31-day (Days 0 to 30) follow-up period after the challenge dose and from the beginning of the long term follow-up up to Year 19;Unsolicited symptoms: during the 31-day (Days 0 to 30) follow-up period after the challenge dose
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Adverse event reporting additional description |
As no challenge dose was administered during Year 16, Year 17 and Year 18 time points, SAEs and other adverse events were not assessed. One subject received the challenge dose at Year 19 for whom the SAEs and other adverse events were assessed during the 31 day period post challenge dose. SAEs were also collected for the entire safety follow-up.
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Assessment type |
Non-systematic | ||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Twinrix Group
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Reporting group description |
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | ||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No subject reported AEs at Years 16, 17, 18. One subject who received the challenge dose at Year 19 experienced 2 AEs: Throat sore and Muscle stiffness; the latter was assessed as casually related to vaccine. These AEs were not of grade 3 intensity. |
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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 | |||
