Clinical Trial Results:
A phase IIIb, open-label, randomised, multicentre study to evaluate the immunogenicity and safety of a booster dose of GlaxoSmithKline Biologicals dTpa-IPV vaccine (Boostrix Polio) compared with Sanofi-Pasteur-MSDs DTPa-IPV (Tetravac), when co-administered with MMRV (Priorix Tetra) in 5 to 6-year-old healthy children.
Summary
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EudraCT number |
2008-006124-64 |
Trial protocol |
IT |
Global end of trial date |
18 Nov 2009
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Results information
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Results version number |
v2 |
This version publication date |
29 Jul 2016
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First version publication date |
20 Feb 2015
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Other versions |
v1 , v3 , v4 |
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 |
111815
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00871000 | ||
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 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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000500-PIP01-08 | ||
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 |
29 Jun 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Nov 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Nov 2009
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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 demonstrate that GSK Biologicals dTpa-IPV vaccine is non-inferior to Sanofi-Pasteur-MSDs DTPa-IPV vaccine, in terms of seroprotection rates against diphtheria, tetanus and poliovirus types 1, 2 and 3, one month after vaccination.
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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 vaccinee remained under medical supervision for 30 minutes after vaccination
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Apr 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 |
Italy: 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) |
303
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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 |
- | |||||||||||||||
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 |
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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Boostrix Polio Group | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Boostrix Polio™
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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 |
Single dose, intramuscular administration at Day 0.
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Investigational medicinal product name |
Priorix Tetra™
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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 |
Subcutaneous use
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Dosage and administration details |
Single dose, subcutaneously at Day 0.
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Arm title
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Tetravac Group | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Priorix Tetra™
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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 |
Subcutaneous use
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Dosage and administration details |
Single dose, subcutaneously at Day 0.
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Investigational medicinal product name |
Tetravac™
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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 |
Single dose, intramuscular administration at Day 0.
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Baseline characteristics reporting groups
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Reporting group title |
Boostrix Polio Group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tetravac Group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Boostrix Polio Group
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Reporting group description |
- | ||
Reporting group title |
Tetravac Group
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Reporting group description |
- |
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End point title |
Anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibody concentrations [1] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 1 Month post-vaccination
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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-poliovirus types 1, 2 and 3 antibody titres [2] | |||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 1 Month post-vaccination
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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-diphtheria (anti-D) and anti-tetanus (anti-T) antibody concentrations above 0.1 IU/mL. | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 1 Month post-vaccination
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Statistical analysis title |
Seroprotection in terms of anti-D antibodies | |||||||||||||||
Statistical analysis description |
To demonstrate that GSK Biologicals’ Boostrix Polio™ vaccine is non-inferior to Sanofi-Pasteur-MSD’s Tetravac™ vaccine, in terms of seroprotection rates against diphtheria, one month after vaccination.
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Comparison groups |
Boostrix Polio Group v Tetravac Group
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Number of subjects included in analysis |
283
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | |||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | |||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-2.61 | |||||||||||||||
upper limit |
2.7 | |||||||||||||||
Notes [3] - Non-inferiority in terms of seroprotection rates against diphtheria was demonstrated if the upper limit of the standardised asymptotic 95% confidence interval (CI) on the group difference [Tetravac Group minus Boostrix Polio Group] in the percentage of subjects with anti-diphtheria antibody concentrations ≥ 0.1 IU/mL was ≤ 10%. |
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Statistical analysis title |
Seroprotection in terms of anti-T antibodies | |||||||||||||||
Statistical analysis description |
To demonstrate that GSK Biologicals’ Boostrix Polio™ vaccine is non-inferior to Sanofi-Pasteur-MSD’s Tetravac™ vaccine, in terms of seroprotection rates against tetanus, one month after vaccination.
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Comparison groups |
Boostrix Polio Group v Tetravac Group
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Number of subjects included in analysis |
283
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | |||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | |||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-2.61 | |||||||||||||||
upper limit |
2.7 | |||||||||||||||
Notes [4] - Non-inferiority in terms of seroprotection rates against tetanus was demonstrated if the upper limit of the standardised asymptotic 95% confidence interval (CI) on the group difference [Tetravac Group minus Boostrix Polio Group] in the percentage of subjects with anti-tetanus antibody concentrations ≥ 0.1 IU/mL was ≤ 10%. |
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End point title |
Number of subjects with anti-poliovirus types 1, 2 and 3 antibody titres above 8 | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At 1 Month post-vaccination
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Statistical analysis title |
Seroprotection in terms of anti-Polio 1 antibodies | ||||||||||||||||||
Statistical analysis description |
To demonstrate that GSK Biologicals’ Boostrix Polio™ vaccine is non-inferior to Sanofi-Pasteur-MSD’s Tetravac™ vaccine, in terms of seroprotection rates against poliovirus type 1, one month after vaccination.
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Comparison groups |
Boostrix Polio Group v Tetravac Group
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Number of subjects included in analysis |
283
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.61 | ||||||||||||||||||
upper limit |
2.7 | ||||||||||||||||||
Notes [5] - Non-inferiority in terms of seroprotection rates against poliovirus type 1 was demonstrated if the upper limit of the standardised asymptotic 95% confidence interval (CI) on the group difference [Tetravac Group minus Boostrix Polio Group] in the percentage of subjects with anti-poliovirus type 1 antibody titers ≥ 8 was ≤ 10%. |
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Statistical analysis title |
Seroprotection in terms of anti-Polio 2 antibodies | ||||||||||||||||||
Statistical analysis description |
To demonstrate that GSK Biologicals’ Boostrix Polio™ vaccine is non-inferior to Sanofi-Pasteur-MSD’s Tetravac™ vaccine, in terms of seroprotection rates against poliovirus type 2, one month after vaccination
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Comparison groups |
Boostrix Polio Group v Tetravac Group
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Number of subjects included in analysis |
283
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Analysis specification |
Pre-specified
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Analysis type |
[6] | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.61 | ||||||||||||||||||
upper limit |
2.7 | ||||||||||||||||||
Notes [6] - Non-inferiority in terms of seroprotection rates against poliovirus type 2 was demonstrated if the upper limit of the standardised asymptotic 95% confidence interval (CI) on the group difference [Tetravac Group minus Boostrix Polio Group] in the percentage of subjects with anti-poliovirus type 2 antibody titers ≥ 8 was ≤ 10%. |
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Statistical analysis title |
Seroprotection in terms of anti-Polio 3 antibodies | ||||||||||||||||||
Statistical analysis description |
To demonstrate that GSK Biologicals’ Boostrix Polio™ vaccine is non-inferior to Sanofi-Pasteur-MSD’s Tetravac™ vaccine, in terms of seroprotection rates against poliovirus type 3, one month after vaccination
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Comparison groups |
Boostrix Polio Group v Tetravac Group
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Number of subjects included in analysis |
283
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [7] | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.61 | ||||||||||||||||||
upper limit |
2.72 | ||||||||||||||||||
Notes [7] - Non-inferiority in terms of seroprotection rates against poliovirus type 1 was demonstrated if the upper limit of the standardised asymptotic 95% confidence interval (CI) on the group difference [Tetravac Group minus Boostrix Polio Group] in the percentage of subjects with anti-poliovirus type 3 antibody titers ≥ 8 was ≤ 10%. |
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End point title |
Anti-pertussis toxoid (anti-PT), anti-filamentous hemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects with anti-D and anti-T antibody concentrations ≥ 1.0 IU/mL | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of seropositive subjects for anti-measles, anti-mumps, anti-rubella and anti-varicella. | |||||||||||||||||||||
End point description |
Seropositivity was defined as subjects with antibody concentrations: ≥ 150 milli-international units per milliliter (mIU/mL), ≥ 231 units per milliliter (U/mL), ≥ 4 international units per milliliter (IU/mL) and ≥ 50 mIU/mL for anti-measles, anti-mumps, anti-rubella and anti-varicella antibodies, respectively.
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Anti-PT, anti-FHA and anti-PRN antibody concentrations | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Anti-measles and anti-varicella antibody concentrations. | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects with booster responses to anti-diphtheria and anti-tetanus. | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects with booster responses to anti-poliovirus types 1, 2 and 3. | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects with booster responses to anti-PT, anti-FHA and anti-PRN. | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of seroconverted subjects for anti-measles, anti-mumps, anti-rubella and anti-varicella | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Number of subjects with any solicited local symptoms. | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects with any solicited general symptoms. | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0-3) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects with any unsolicited adverse events (AEs). | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the 31 days (Days 0-30) post-vaccination period
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No statistical analyses for this end point |
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End point title |
Number of subjects with serious adverse events (SAEs). | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
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End point timeframe |
During the whole study period
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No statistical analyses for this end point |
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End point title |
Anti-mumps antibody concentrations. | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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No statistical analyses for this end point |
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End point title |
Anti-rubella antibody concentrations. | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Secondary
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End point timeframe |
At 1 Month post-vaccination
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|
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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 |
Solicited symptoms: 4-day follow-up period after vaccination (Day 0 - Day 3); Unsolicited AEs: 31-day follow-up period after vaccination (Day 0 - Day 30); SAEs: throughout the study.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13
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Reporting groups
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Reporting group title |
Boostrix Group
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tetravac Group
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |