Clinical Trial Results:
Safety and Immunogenicity of Tdap Vaccine Compared to DTaP vaccine as Fifth Dose Booster in Children 4 to 6 Years of Age
Summary
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EudraCT number |
2015-003500-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
16 Oct 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Feb 2016
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First version publication date |
19 Feb 2016
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Other versions |
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 |
Td517
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00467519 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Sanofi Pasteur Inc.
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Sponsor organisation address |
1 Discovery Drive, Swiftwater, United States, 18370
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Public contact |
Medical Team Leader, Scientific and Medical Affairs Department, Sanofi Pasteur Inc., 1 570-957-5433, vitali.pool@sanofipasteur.com
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Scientific contact |
Medical Team Leader, Scientific and Medical Affairs Department, Sanofi Pasteur Inc., 1 570-957-5433, vitali.pool@sanofipasteur.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 |
16 Dec 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Oct 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 |
1) To compare the immune responses of Tdap to DTaP vaccine when each is administered as a 5th dose to DAPTACEL- or Pentacel-primed subjects and given concurrently, but in a separate arm from poliomyelitis, measles, mumps, rubella (MMR) and varicella vaccines to children aged 4 to 6 years, as measured by seroprotection rates (≥ 0.1 IU/mL), serothreshold rates (≥ 1.0 IU/mL) and booster response rates for diphtheria and tetanus.
2) To compare immune responses of Tdap to DTaP vaccine when administered as a 5th dose to DAPTACEL- or Pentacel-primed subjects and given concurrently, but in a separate arm from poliomyelitis, measles, mumps, rubella (MMR) and varicella vaccines to children aged 4 to 6 years, as measured by booster response rates and GMTs for pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN] and fimbriae types 2 and 3 [FIM]).
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
13 Apr 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 |
Canada: 18
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Country: Number of subjects enrolled |
United States: 1024
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Worldwide total number of subjects |
1042
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EEA total number of subjects |
0
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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) |
1042
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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 |
Subjects were enrolled from 13 April 2007 to 16 October 2009 in 42 clinical centers in the United States and 1 clinical center in Canada. | |||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 1042 subjects who met the inclusion and exclusion criteria were enrolled and vaccinated. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||||||||||||||
Blinding implementation details |
The subject, Investigator, study site and sponsor personnel were blinded to the vaccine administered, except for an unblinded study nurse who administered the vaccines and the site monitors. To maintain the blind, the unblinded nurse did not participate in the collection of safety data. The randomization code was generated by the Sponsor and was kept in a secured filed at the Sponsor's site. The Investigator and health authorities could request code breaking for an SAE, if required, by protocol.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Tdap Vaccine Group | |||||||||||||||||||||
Arm description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap). | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap)
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Investigational medicinal product code |
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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 |
0.5 mL, intramuscular, 1 injection on Day 0.
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Investigational medicinal product name |
Poliovirus Vaccine Inactivated (IPV)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use, Subcutaneous use
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Dosage and administration details |
0.5 mL, intramuscular or subcutaneous, 1 injection on Day 0.
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Investigational medicinal product name |
Measles, Mumps and Rubella Virus Vaccine Live (MMR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous, administered as either 1 injection alone in combination with varicella vaccine
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Investigational medicinal product name |
Varicella Virus Vaccine Live (Varicella vaccine)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous, administered as either 1 injection alone or in combination with MMR vaccine.
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Arm title
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DTaP Vaccine Group | |||||||||||||||||||||
Arm description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of diphtheria, tetanus and acellular pertussis vaccine (DTaP). | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Diphtheria, Tetanus, and Acellular Pertussis Vaccine (DTaP)
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Investigational medicinal product code |
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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 |
0.5 mL, intramuscular, 1 injection on Day 0.
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Investigational medicinal product name |
Poliovirus Vaccine Inactivated (IPV)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use, Subcutaneous use
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Dosage and administration details |
0.5 mL, intramuscular or subcutaneous, 1 injection on Day 0.
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Investigational medicinal product name |
Measles, Mumps and Rubella Virus Vaccine Live (MMR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous, administered as either 1 injection alone in combination with varicella vaccine
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Investigational medicinal product name |
Varicella Virus Vaccine Live (Varicella vaccine)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous, administered as either 1 injection alone or in combination with MMR vaccine.
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Baseline characteristics reporting groups
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Reporting group title |
Tdap Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DTaP Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of diphtheria, tetanus and acellular pertussis vaccine (DTaP). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tdap Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap). | ||
Reporting group title |
DTaP Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of diphtheria, tetanus and acellular pertussis vaccine (DTaP). |
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End point title |
Percentage of Subjects Who Achieved Seroprotection at Baseline and 30 Days Post-vaccination for Diphtheria and Tetanus at ≥ 0.1 IU/mL Level [1] | ||||||||||||||||||||||||
End point description |
Seroprotection rate of level ≥ 0.1 IU/mL was defined as antibody concentrations ≥ 0.1 IU/mL. Diphtheria titers were determined by toxin neutralization assay; tetanus titers were determined by enzyme-linked immunosorbent assay (ELISA).
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End point type |
Primary
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End point timeframe |
Pre-dose and 30 days 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Who Achieved Serothreshold at Baseline and 30 Days Post-vaccination for Diphtheria and Tetanus at Level ≥ 1.0 IU/mL [2] | ||||||||||||||||||||||||
End point description |
Serothreshold rate at level ≥ 1.0 IU/mL was defined as antibody concentrations ≥ 1.0 IU/mL. Diphtheria titers were determined by toxin neutralization assay; tetanus titers were determined by enzyme-linked immunosorbent assay (ELISA).
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End point type |
Primary
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End point timeframe |
Pre-dose and 30 days 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Who Demonstrated Booster Response at 30 Days Post-vaccination for Pertussis [3] | ||||||||||||||||||||||||
End point description |
Booster response was defined as post-titer ≥ 0.4 IU/mL and pre-titer < 0.1 IU/mL, or Post-/Pre-titer ≥ 4 increase and pre-titer ≥ 0.1 IU/mL but < 2 IU/mL, or Post-/Pre-titer ≥ 2 increase and pre-titer ≥ 2 IU/mL.
Post-vaccination titers for pertussis toxoid (PT), pertussis filamentous hemagglutinin (FHA), pertussis pertactin (PRN), and pertussis fimbriae types 2 and 3 (FIM) were determined by enzyme-linked immunosorbent assay (ELISA).
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End point type |
Primary
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End point timeframe |
30 days post-vaccination
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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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Who Demonstrated Booster Response at 30 Days Post-vaccination for Diphtheria and Tetanus [4] | ||||||||||||||||||
End point description |
Booster response was defined as post-titer ≥ 0.4 IU/mL and pre-titer < 0.1 IU/mL, or Post-/Pre-titer ≥ 4 increase and pre-titer ≥ 0.1 IU/mL but < 2 IU/mL, or Post-/Pre-titer ≥ 2 increase and pre-titer ≥ 2 IU/mL.
Post-vaccination titers for diphtheria was determined by neutralization assay; tetanus titers were determined by enzyme-linked immunosorbent assay (ELISA).
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End point type |
Primary
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End point timeframe |
30 days post-vaccination
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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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titers (GMTs) at Baseline and 30 Days Post-vaccination for Pertussis [5] | ||||||||||||||||||||||||||||||||||||
End point description |
Pre- and post-vaccination GMTs and their 95% confidence intervals for pertussis toxoid (PT), pertussis filamentous hemagglutinin (FHA), pertussis pertactin (PRN), and pertussis fimbriae types 2 and 3 (FIM) were determined by enzyme-linked immunosorbent assay (ELISA).
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End point type |
Primary
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End point timeframe |
Pre-dose and 30 days post-vaccination
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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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects Reporting at Least 1 Solicited Injection Site or Solicited Systemic Reaction Post-vaccination | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site reactions: Pain, Erythema/Redness, Swelling, and Increased limb circumference (both arms). Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 injection site reactions: Pain, Incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism; Erythema/Redness and Swelling, > 50 mm; Limb circumference, > 40 mm increase over pre-vaccination measurement. Grade 3 systemic reactions: Fever, >39.5°C (> 103.1°F); Headache, Malaise, and Myalgia, Prevents daily activities.
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End point type |
Other pre-specified
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End point timeframe |
Days 0 to 7 post-vaccination
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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 |
Adverse event data were collected from the day of vaccination to 6 months post-vaccination.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11
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Reporting groups
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Reporting group title |
Tdap Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DTaP Vaccine Group
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Reporting group description |
Subjects 4 to 6 years of age who had previously received 4 doses of Pentacel or DAPTACEL received a booster dose of diphtheria, tetanus and acellular pertussis vaccine (DTaP). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [8] - 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: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. |
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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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26 Oct 2007 |
Study design rationale, inclusion criteria, randomization, and power calculations were updated; a Canadian site was added; 7 year long-term immunogenicity assessment was removed; new product batch numbers were added, archiving procedures were updated, indications for the investigational product were revised; and clarification was made on site practices, blinding/unblinding procedures, and storage conditions. |
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24 Feb 2009 |
Primary objectives and sample size were revised; vaccine dosing and indications were updated; study period was extended; references to 3-year follow up were removed; non-inferiority margins were updated; and storage and shipment conditions were further clarified. |
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19 May 2009 |
Changes were made regarding interim analysis of data, antibody assessment, evaluation of immune responses, and collection of blood samples; consent form was also updated with postmarketing information. |
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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 |