Diphtheria, Pertussis, Tetanus
Conditions
Keywords
Tetanus,, Diphtheria,, Pertussis
Brief summary
Objectives: To provide safety data on revaccination with ADACEL® vaccine. To describe the immune response to tetanus, diphtheria, and pertussis antigens following revaccination with ADACEL® vaccine 4-5 years after first vaccination.
Interventions
BIOLOGICALTetanus-diphtheria-acellular pertussis (Tdap) vaccine
0.5mL, Intramuscular (IM)
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
* Previously received ADACEL vaccine as part of Aventis Pasteur studies Td501, Td502, or Td505. * At least 15 but no greater than 69 years of age at the time of vaccination in this trial. * Signed Institutional Review Board (IRB)-approved informed assent / consent form. * Able to attend all scheduled visits and to comply with all trial procedures. * For a woman, inability to become pregnant or negative serum/urine pregnancy test.
Exclusion criteria
* Any condition which, in the opinion of the investigator, would pose a health risk to the participant or interfere with the evaluation of the vaccine. * Serious chronic disease (ie, cardiac, renal, neurologic, metabolic, rheumatologic, psychiatric) that is unstable or that might: * interfere with the ability to participate fully in the study; or * interfere with evaluation of the vaccine. * Known or suspected impairment of immunologic function. * Febrile illness within the last 72 hours or an oral temperature ≥100.4°F (≥38°C) at the time of inclusion. * History of documented tetanus, diphtheria or pertussis disease within the preceding 5 years. * Known or suspected receipt of a tetanus-, diphtheria- or pertussis-containing vaccine since participation in Study Td501, Td502, or Td505. (Receipt of Menactra vaccine at any time prior to the present study is permitted, subject to the next exclusion criterion). * Received any vaccine, other than influenza vaccine, in the 28-day period prior to enrollment or scheduled to receive any vaccine, other than influenza vaccine, in the 28-day period after enrollment. For influenza vaccine only, defer if received in the 14-day period prior to enrollment or scheduled to receive in the 14-day period after enrollment * Administration of immune globulin or other blood products within the last three months, or injected or oral corticosteroids or other immunomodulator therapy within six weeks of the study vaccine. Individuals on a tapering dose schedule of oral steroids lasting less than 7 days may be included in the trial as long as they have not received more than one course within the last two weeks prior to enrollment. * Suspected or known hypersensitivity to any of the vaccine components or to latex. * Unable to attend the scheduled visits or to comply with the study procedures. * In females of childbearing potential, a positive or equivocal urine pregnancy test at enrollment. * Nursing mother. * Participation in another interventional clinical trial in the 4 weeks preceding enrollment or planning to participate in another interventional clinical trial during the planned period of this study. * Current abuse of alcohol or drug addiction that may interfere with the subject's ability to comply with trial visits or procedures. * Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination. * Subject deprived of freedom by an administrative or court order, or under the stress of an emergency setting, or hospitalized without his/her consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | 0-14 days post-vaccination | Solicited Injection Site Reactions: Pain, Erythema/Redness, Swelling. Solicited Systemic Reactions: Fever (Temperature), Headache, Myalgia, Malaise. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Day 28 post-vaccination | Pre- and post-vaccination GMTs and their 95% confidence intervals for diphtheria were determined by toxin neutralization testing; the other antibody levels were determined by enzyme-linked immunosorbent assay testing. |
| Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Day 28 post-vaccination | Pre- and post-vaccination GMTs and their 95% confidence intervals for Pertussis were determined by enzyme-linked immunosorbent assay testing. |
| Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Day 28 post-vaccination | Seroprotection: Tetanus or diphtheria titer ≥ 0.1 after Adacel® vaccination. Tetanus titers determined by enzyme-linked immunosorbent assay; diphtheria titers determined by toxin neutralization assay. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were enrolled from 21 August 2006, to 12 April 2007, in 6 clinical centers in the US and 6 clinical centers in Canada.
Pre-assignment details
A total of 545 participants were enrolled and vaccinated in the study. Data on 544 participants that met the inclusion and exclusion criteria were analyzed and reported. One participant who did not receive Adacel® vaccine in one of the previous studies was excluded from the Safety Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| Adacel® Vaccine Group Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518. | 544 |
| Total | 544 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Adacel® Vaccine Group |
|---|---|
| Age, Categorical <=18 years | 169 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 368 Participants |
| Age Continuous | 31.7 Years STANDARD_DEVIATION 15.7 |
| Region of Enrollment Canada | 350 participants |
| Region of Enrollment United States | 194 participants |
| Sex: Female, Male Female | 284 Participants |
| Sex: Female, Male Male | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 479 / 544 |
| serious Total, serious adverse events | 7 / 544 |
Outcome results
Primary
Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination
Solicited Injection Site Reactions: Pain, Erythema/Redness, Swelling. Solicited Systemic Reactions: Fever (Temperature), Headache, Myalgia, Malaise.
Time frame: 0-14 days post-vaccination
Population: Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population.~The solicited systemic reaction, malaise was not collected in the previous studies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Solicited Injection Site Reaction | 89 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Injection Site Pain | 88 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Injection Site Pain (Incapacitating) | 2 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Injection Site Erythema/Redness | 29 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Injection Site Erythema/Redness (≥ 5 cm) | 3 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Injection Site Swelling | 26 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Injection Site Swelling (≥ 5 cm) | 3 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Fever | 7 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Fever (> 39.0 ºC or > 102.2 ºF) | 1 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Headache | 53 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Headache (Prevents daily activities) | 3 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Myalgia | 61 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Myalgia (Prevents daily activities) | 4 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Any Malaise | 38 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination | Grade 3 Malaise (Prevents daily activities) | 3 Percentage of Participants |
Other Pre-specified
Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination.
Pre- and post-vaccination GMTs and their 95% confidence intervals for Pertussis were determined by enzyme-linked immunosorbent assay testing.
Time frame: Day 28 post-vaccination
Population: Geometric mean titers were assessed in the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis FIM (EU/mL) Pre-Dose, n = 445 | 165 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis PT (EU/mL) Pre-Dose, n = 381 | 21.3 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis PT (EU/mL) Post-Dose, n = 425 | 104 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis FHA (EU/mL) Pre-Dose, n = 450 | 34.6 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis FHA (EU/mL) Post-Dose, n = 450 | 201 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis PRN (EU/mL) Pre-Dose, n = 451 | 37.3 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis PRN (EU/mL) Post-Dose, n = 451 | 218 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. | Pertussis FIM (EU/mL) Post-Dose, n = 450 | 749 Titers |
Other Pre-specified
Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination.
Pre- and post-vaccination GMTs and their 95% confidence intervals for diphtheria were determined by toxin neutralization testing; the other antibody levels were determined by enzyme-linked immunosorbent assay testing.
Time frame: Day 28 post-vaccination
Population: Geometric mean titers were assessed in the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Tetanus (IU/mL) Pre-Dose, n = 445 | 1.41 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Tetanus (IU/mL) Post-Dose, n = 445 | 9.62 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Diphtheria (IU/mL) no Menactra Pre-Dose, n = 379 | 0.133 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Diphtheria (IU/mL) no Menactra Post-Dose n = 379 | 2.17 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Diphtheria (IU/mL) with Menactra Pre-Dose n = 64 | 4.45 Titers |
| Adacel® Vaccine Group | Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. | Diphtheria (IU/mL) with Menactra Post-Dose n = 64 | 8.70 Titers |
Other Pre-specified
Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel®
Seroprotection: Tetanus or diphtheria titer ≥ 0.1 after Adacel® vaccination. Tetanus titers determined by enzyme-linked immunosorbent assay; diphtheria titers determined by toxin neutralization assay.
Time frame: Day 28 post-vaccination
Population: Tetanus and diphtheria antibody analyses were in all enrolled and vaccinated participants in the per-protocol population. Diphtheria antibody titers were analyzed separately for participants without and with an intervening Menactra vaccination between the previous study and Study Td518.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Tetanus (IU/mL) Pre-Dose | 96 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Tetanus (IU/mL) Post-Dose | 100 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Diphtheria (IU/mL) without Menactra, Pre-Dose | 61 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Diphtheria (IU/mL) without Menactra, Post-Dose | 95 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Diphtheria (IU/mL) Menactra, Pre-Dose | 95 Percentage of Participants |
| Adacel® Vaccine Group | Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® | Diphtheria (IU/mL) Menactra, Post-Dose | 100 Percentage of Participants |