Clinical Trial Results:
One-, Three-, Five-, and Ten-Year Data on the Long-Term Immunogenicity of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) in Adults and Adolescents (11-64 years)
Summary
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EudraCT number |
2015-005845-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
29 Aug 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Apr 2016
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First version publication date |
16 Apr 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 |
Td506-LT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Sanofi Pasteur Limited
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Sponsor organisation address |
1755 Steeles Ave. West, Toronto, Canada, M2R 3T4
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Public contact |
Clinical/Medical Monitor, Sanofi Pasteur, 1 570-957-1506, Dr.Johnson@sanofipasteur.com
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Scientific contact |
Clinical/Medical Monitor, Sanofi Pasteur, 1 570-957-1506, Dr.Johnson@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? |
Yes
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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 |
Final
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Date of interim/final analysis |
29 Aug 2012
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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 |
29 Aug 2012
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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 |
Long-term follow-up study to describe the profile of antibody levels after booster vaccination with Tdap vaccine or Td vaccine at 1-month, 1-, 3-, and 5-years postvaccination and Tdap only at 10 years post-vaccination.
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Protection of trial subjects |
Subjects were vaccinated in a previous study, Td506. No vaccination was administered as part of this long-term immunogenicity study.
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Background therapy |
A subset (189) of the Per-Protocol Immunogenicity (PPI) Paired Population from the Tdap vaccine group (2296 subjects) in the main study were in the 10-year follow up immunogenicity follow-up analysis. The Per-Protocol Immunogenicity (PPI) Paired Population for the 10-year follow-up analyses included subjects from the PPI-1 year, PPI-3 year, PPI-5 year, and PPI-10 year populations who provided blood samples at all 4 follow-up visits, i.e., at 1, 3, 5, and 10 years, and who did not receive any diphtheria-, tetanus-,or pertussis-containing vaccine between 1-month and 10-years after vaccination or did not report pertussis illness during this period. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
28 Aug 2002
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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 |
United States: 189
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Worldwide total number of subjects |
189
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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) |
0
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Adolescents (12-17 years) |
44
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Adults (18-64 years) |
145
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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 |
A subset of the Per-Protocol Immunogenicity (PPI) Paired Population from the Tdap vaccine group in the main study were in the 10-year follow up immunogenicity follow-up study. | ||||||
Pre-assignment
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Screening details |
A subset (189) of the Tdap vaccine group in the original study (paired per-protocol population) were included in the 10-year long-term immunogenicity analysis. | ||||||
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 |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Tdap Vaccine | ||||||
Arm description |
A subset of subjects (paired per-protocol population) that received 1 dose of Tdap vaccine (Adacel®) in the original Td506 study. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Adacel®)
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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 |
No vaccine was administered in the long-term follow-up study. (Subjects received 1 injection, 0.5 mL by intramuscular route on Day 0 in the original Td506 study)
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Baseline characteristics reporting groups
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Reporting group title |
Tdap Vaccine
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Reporting group description |
A subset of subjects (paired per-protocol population) that received 1 dose of Tdap vaccine (Adacel®) in the original Td506 study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tdap Vaccine
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Reporting group description |
A subset of subjects (paired per-protocol population) that received 1 dose of Tdap vaccine (Adacel®) in the original Td506 study. |
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End point title |
Percentage of Subjects with Seroprotection to Tetanus and Diphtheria Following Vaccination with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) - ADACEL® [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-Diphtheria antibody responses were measured by the ability of the test sera to protect Vero cells from a diphtheria toxin challenge. Anti-Tetanus antibody responses were measured by an indirect enzyme-linked immunosorbent assay method. Seroprotection was defined as diphtheria and tetanus titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL.
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End point type |
Primary
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End point timeframe |
Day 0 (pre-vaccination) and 1 month and 1, 3, 5, 10 years 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 vaccine groups from the primary series for the long term follow-up period. |
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Notes [2] - N represents the PPI Paired population subset. |
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No statistical analyses for this end point |
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End point title |
Summary of Geometric Mean Concentrations of Anti-Tetanus and Anti-Diphtheria Titers Following Vaccination with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) - ADACEL® | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-Diphtheria antibody responses were measured by the ability of the test sera to protect Vero cells from a diphtheria toxin challenge. Anti-Tetanus antibody responses were measured by an indirect enzyme-linked immunosorbent assay method.
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End point type |
Other pre-specified
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End point timeframe |
Day 0 (pre-vaccination) and 1 month and 1, 3, 5, 10 years post-vaccination
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Notes [3] - N represents the PPI Paired population subset. |
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No statistical analyses for this end point |
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End point title |
Summary of Geometric Mean of Anti-Pertussis Titers Following Vaccination with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) - ADACEL® | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-Pertussis Toxoid (PT), anti-Filamentous hemagglutinin (FHA), anti-Fimbriae (FIM), and anti-Pertactin (PRN) immunoglobulin antibody titers were determined by an indirect ELISA method.
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End point type |
Other pre-specified
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End point timeframe |
Day 0 (pre-vaccination) and 1 month and 1, 3, 5, 10 years post-vaccination
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Notes [4] - N represents the PPI Paired population subset. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Seropositivity to Pertussis antigens Following Vaccination with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) - ADACEL® | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-Pertussis Toxoid (PT), anti-Filamentous hemagglutinin (FHA), anti-Fimbriae (FIM), and anti-Pertactin (PRN) immunoglobulin antibody titers were determined by an indirect ELISA method. Seropositivity ≥ 4X lower limit of quantitation (LLOQ) was ≥ 16 EU/mL for PT, FIM, and PRN and ≥ 12 EU/mL for FHA.
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End point type |
Other pre-specified
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End point timeframe |
Day 0 (pre-vaccination) and 1 month and 1, 3, 5, 10 years post-vaccination
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Notes [5] - N represents the PPI Paired population subset. |
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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 |
This long-term immunogenicity study was a follow-up to study Td506 which evaluated the safety and immunogenicity of Tdap compared to Td vaccine. No vaccines were administered in this study and adverse event data were also not collected.
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Assessment type |
Non-systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
10
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Frequency threshold for reporting non-serious adverse events: 5% | |||
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: This long-term immunogenicity study was a follow-up to study Td506 which evaluated the safety and immunogenicity of Tdap compared to Td vaccine. No vaccines were administered in this study and adverse event data were also not collected. |
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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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23 Jul 2001 |
Involved study design changes to increase the safety database, subject follow-up duration, and included administrative changes for clarification. |
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30 Apr 2002 |
Added the long-term follow up for 1 year. |
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10 Jun 2004 |
Planned long-term follow up for 3 years and 5 years. |
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30 Sep 2005 |
Planned long-term follow up for 10 years. |
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15 Jun 2006 |
Updated study personnel throughout the protocol. |
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11 Jul 2011 |
Involved study design changes to increase the safety database, subject follow-up duration, and included administrative changes for clarification. |
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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 |