Diphtheria, Pertussis, Tetanus, Whooping Cough
Conditions
Keywords
Adacel vaccine, Tetanus, Diphtheria, whooping cough
Brief summary
The purpose of this study is to describe the safety and immunogenicity of repeat administration of Adacel vaccine approximately 10 years following initial administration of the vaccine. Antibody levels prior to revaccination will also be used to characterize antibody persistence following initial vaccination 10 years earlier. Primary Objectives: * To compare seroprotection rates against tetanus and diphtheria induced by Adacel vaccine to those induced by Td Adsorbed vaccine. * To compare booster response rates against tetanus and diphtheria induced by Adacel vaccine to those induced by Td Adsorbed vaccine. * To compare anti-pertussis geometric mean antibody concentrations (GMCs) induced by Adacel vaccine to the GMCs induced by Daptacel® vaccine given to infants. Secondary Objectives: * To describe the rates of immediate reactions, solicited reactions, unsolicited adverse events (AEs), and serious adverse events (SAEs) following vaccination with Adacel or Td Adsorbed vaccine. * To describe booster response rates for pertussis antigens following revaccination with Adacel vaccine.
Detailed description
Healthy adults \< 65 years of age who received Adacel vaccine 10 years previously will be randomized to receive either Adacel or TENIVAC (Td Adsorbed) vaccine. They will be assessed for immunogenicity at baseline and post-vaccination. Safety data will be collected for 6 months following vaccination.
Interventions
BIOLOGICALTetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine
0.5 mL, Intramuscular
BIOLOGICALTetanus and Diphtheria Toxoids Adsorbed For Adult Use
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is ≥ 18 to \< 65 years of age at the time of vaccination. * Received Adacel vaccine no less than 9 and no more than 11 years previously. * Informed consent form has been signed and dated. * Subject is able to attend all scheduled visits and to comply with all trial procedures.
Exclusion criteria
* Subject is pregnant, or lactating, or of child bearing potential without using an effective method of contraception or not practicing abstinence for at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination. Females who are pre-menarche or post-menopausal for at least one year, or surgically sterile will not be excluded. * Any condition that, in the opinion of the Investigator, would pose a health risk to the participant or interfere with the evaluation of the vaccine. * Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion. * Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). * Known or suspected receipt of tetanus toxoid (T), tetanus and diphtheria toxoids (Td), or tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine since receipt of the qualifying dose of Adacel vaccine described in Inclusion Criterion #2. * A personal history of physician-diagnosed or laboratory-confirmed pertussis disease within the last 10 years. * A previous severe reaction to pertussis, diphtheria or tetanus vaccine including immediate anaphylaxis, encephalopathy within 7 days or seizure within 3 days of receiving the vaccine. * Receipt of immune globulins, blood or blood-derived products in the past 3 months. * Suspected or known hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances. * Receipt of any vaccine within 30 days before receiving study vaccine, or plans to receive another vaccine before the 2nd visit; except that influenza vaccine may have been received between 30 and 15 days (but no less than 15 days) before receiving study vaccine. * Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the first study vaccination or during the course of the study, at the discretion of the Sponsor. * Seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C, as reported by the subject. * Laboratory-confirmed thrombocytopenia, which may be a contraindication for IM vaccination, at the discretion of the Investigator. * Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular (IM) vaccination, at the discretion of the Investigator. * Personal history of Guillain-Barré syndrome. * Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of vaccination. A prospective subject should not be enrolled in the study until the condition has resolved or the febrile event has subsided. * Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study. * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. * Current alcohol or drug use that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Diphtheria and Tetanus Seroprotection | 1 month post-booster vaccination | Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. Seroprotection was defined as the following: Anti-Diphtheria and Anti-Tetanus ≥ 0.1 IU/mL. |
| Percentage of Participants With Diphtheria and Tetanus Booster Response | 1 month post-booster vaccination | Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. A booster response was defined as a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with pre-vaccination antibody concentrations ≤2.56 IU/mL for diphtheria and ≤ 2.7 IU/mL for tetanus. If the pre vaccination antibody concentrations were \> 2.56 IU/mL for diphtheria and \> 2.7 IU/mL for tetanus, then a 2-fold increase in response rate was defined as a booster response. |
| Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies | 1 month post-booster vaccination | Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin (FHA), Pertactin, Fimbriae types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Anti-pertussis GMCs further to Adacel vaccination was compared to an historical control group with Daptacel (NCT00255047 for pertussis toxoid and PMID 8538705 for FHA, Pertactin and Fimbriae) since Td Adsorbed Vaccine does not contain any pertussis antigens. |
| Percentage of Subjects With Pertussis Antigen Booster Response | 1 month post-booster vaccination | Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin \[FHA\], Pertactin, Fimbriae (types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Booster response is defined as a minimum rise in antibody concentration from pre- to post-vaccination. The minimum rise is at least 2 times if the pre-vaccination concentration is above the cutoff value, or at least 4 times if it is at or below the cutoff value. Anti-pertussis toxoid booster response rates further to Adacel vaccination was compared to an expected booster rates based on study Td506 (PMID 15933223) since Td Adsorbed Vaccine does not contain any pertussis antigens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Day 0 up to Day 7 post-vaccination | Injection site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection site reactions: Pain, Significant, prevents daily activity. Erythema and Swelling, \>100 mm. Grade 3 Systemic reactions: Fever, ≥39°C or ≥102.1 F; Headache, Malaise, and Myalgia, Significant; prevents daily activity. |
Countries
Canada, United States
Participant flow
Recruitment details
Study participants were enrolled from 30 November 2011 to 13 August 2015 at 31 clinic sites in the United States and 2 clinic sites in Canada.
Pre-assignment details
A total of 1330 participants who met all inclusion criteria and no exclusion criteria were randomized; 1327 participants were vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Adacel Vaccine Healthy adults \<65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine. | 1,002 |
| Td Adsorbed Vaccine Healthy adults \<65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine). | 328 |
| Total | 1,330 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 1 |
Baseline characteristics
| Characteristic | Adacel Vaccine | Td Adsorbed Vaccine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1002 Participants | 328 Participants | 1330 Participants |
| Age, Continuous Age Continuous | 28.9 Years STANDARD_DEVIATION 10 | 29.2 Years STANDARD_DEVIATION 10.6 | 29 Years STANDARD_DEVIATION 10.3 |
| Region of Enrollment Canada | 732 Participants | 244 Participants | 976 Participants |
| Region of Enrollment United States | 270 Participants | 84 Participants | 354 Participants |
| Sex: Female, Male Female | 646 Participants | 212 Participants | 858 Participants |
| Sex: Female, Male Male | 356 Participants | 116 Participants | 472 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 999 | 0 / 328 |
| other Total, other adverse events | 855 / 999 | 284 / 328 |
| serious Total, serious adverse events | 8 / 999 | 1 / 328 |
Outcome results
Primary
Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies
Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin (FHA), Pertactin, Fimbriae types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Anti-pertussis GMCs further to Adacel vaccination was compared to an historical control group with Daptacel (NCT00255047 for pertussis toxoid and PMID 8538705 for FHA, Pertactin and Fimbriae) since Td Adsorbed Vaccine does not contain any pertussis antigens.
Time frame: 1 month post-booster vaccination
Population: Geometric mean concentrations were assessed in the Per Protocol Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Adacel Vaccine | Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies | FHA | 209 Concentrations (1/dil) |
| Adacel Vaccine | Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies | Pertactin | 318 Concentrations (1/dil) |
| Adacel Vaccine | Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies | Pertussis Toxoid | 102 Concentrations (1/dil) |
| Adacel Vaccine | Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies | Fimbriae types 2 and 3 | 745 Concentrations (1/dil) |
Comparison: Comparison of anti-pertussis toxoid GMCs between Adacel and historical control groups95% CI: [0.92, 1.18]
Comparison: Comparison of the anti-FHA GMCs between Adacel and historical Control groups95% CI: [4.51, 6.05]
Comparison: Comparison of the anti-Pertactin GMCs between Adacel and historical Control groups95% CI: [2.46, 3.51]
Comparison: Comparison of the post-vaccination anti-Fimbriae (types 2 and 3) GMCs between Adacel and historical Control groups95% CI: [1.84, 2.6]
Primary
Percentage of Participants With Diphtheria and Tetanus Booster Response
Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. A booster response was defined as a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with pre-vaccination antibody concentrations ≤2.56 IU/mL for diphtheria and ≤ 2.7 IU/mL for tetanus. If the pre vaccination antibody concentrations were \> 2.56 IU/mL for diphtheria and \> 2.7 IU/mL for tetanus, then a 2-fold increase in response rate was defined as a booster response.
Time frame: 1 month post-booster vaccination
Population: Booster response rates were assessed in the Per Protocol Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel Vaccine | Percentage of Participants With Diphtheria and Tetanus Booster Response | Tetanus | 74.5 Percentage of participants |
| Adacel Vaccine | Percentage of Participants With Diphtheria and Tetanus Booster Response | Diphtheria | 83.2 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants With Diphtheria and Tetanus Booster Response | Tetanus | 81.6 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants With Diphtheria and Tetanus Booster Response | Diphtheria | 84.1 Percentage of participants |
Comparison: Comparison of the anti-tetanus booster response rates between the two groups95% CI: [-12, -1.7]
Comparison: Comparison of the anti-diphteria booster response rates between the two groups95% CI: [-5.4, 4]
Primary
Percentage of Participants With Diphtheria and Tetanus Seroprotection
Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. Seroprotection was defined as the following: Anti-Diphtheria and Anti-Tetanus ≥ 0.1 IU/mL.
Time frame: 1 month post-booster vaccination
Population: Seroprotection was assessed in the Per Protocol Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel Vaccine | Percentage of Participants With Diphtheria and Tetanus Seroprotection | Tetanus | 100.0 Percentage of participants |
| Adacel Vaccine | Percentage of Participants With Diphtheria and Tetanus Seroprotection | Diphtheria | 99.8 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants With Diphtheria and Tetanus Seroprotection | Tetanus | 100.0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants With Diphtheria and Tetanus Seroprotection | Diphtheria | 99.4 Percentage of participants |
Comparison: Comparison of anti-tetanus seroprotection rate between the two groups95% CI: [-0.4, 1.2]
Comparison: Comparison of anti-diphtheria seroprotection rates between the two groups95% CI: [-0.3, 2.1]
Primary
Percentage of Subjects With Pertussis Antigen Booster Response
Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin \[FHA\], Pertactin, Fimbriae (types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Booster response is defined as a minimum rise in antibody concentration from pre- to post-vaccination. The minimum rise is at least 2 times if the pre-vaccination concentration is above the cutoff value, or at least 4 times if it is at or below the cutoff value. Anti-pertussis toxoid booster response rates further to Adacel vaccination was compared to an expected booster rates based on study Td506 (PMID 15933223) since Td Adsorbed Vaccine does not contain any pertussis antigens.
Time frame: 1 month post-booster vaccination
Population: Booster response rate was assessed in the Per protocol analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel Vaccine | Percentage of Subjects With Pertussis Antigen Booster Response | Pertussis Toxoid | 77.5 Percentage of subjects |
| Adacel Vaccine | Percentage of Subjects With Pertussis Antigen Booster Response | FHA | 68.9 Percentage of subjects |
| Adacel Vaccine | Percentage of Subjects With Pertussis Antigen Booster Response | Pertactin | 65.3 Percentage of subjects |
| Adacel Vaccine | Percentage of Subjects With Pertussis Antigen Booster Response | Fimbriae (types 2 and 3) | 56.8 Percentage of subjects |
Comparison: comparison of anti-pertussis toxoid booster response rates was performed between the Adacel and historical groups95% CI: [13.27, 18.73]
Comparison: Comparison of the anti-FHA booster response rates between the Adacel and historical groups95% CI: [-7.23, -1.34]
Comparison: Comparison of the anti-Pertactin booster response rates between Adacel and historical groups95% CI: [-21.7, -15.6]
Comparison: Comparison of the anti-Fimbriae (types 2 and 3) booster response rates between Adacel and historical groups95% CI: [-22.3, -16]
Secondary
Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions
Injection site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection site reactions: Pain, Significant, prevents daily activity. Erythema and Swelling, \>100 mm. Grade 3 Systemic reactions: Fever, ≥39°C or ≥102.1 F; Headache, Malaise, and Myalgia, Significant; prevents daily activity.
Time frame: Day 0 up to Day 7 post-vaccination
Population: Solicited injection site and systemic reactions were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Pain | 87.1 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Pain | 3.6 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Erythema | 6.4 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Erythema | 0.2 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Swelling | 6.9 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Swelling | 0.3 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Fever | 0.9 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Fever | 0.2 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Headache | 41.4 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Headache | 2.6 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Malaise | 33.3 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Malaise | 3.0 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Myalgia | 58.1 Percentage of participants |
| Adacel Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Myalgia | 3.0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Malaise | 30.8 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Pain | 87.4 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Fever | 0.3 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Pain | 2.8 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Myalgia | 58.2 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Erythema | 5.5 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Headache | 39.1 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Erythema | 0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Malaise | 3.7 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Injection site Swelling | 8.0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Headache | 4.0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Injection site Swelling | 0 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Grade 3 Myalgia | 3.1 Percentage of participants |
| Td Adsorbed Vaccine | Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions | Any Fever | 1.8 Percentage of participants |