Diphtheria, Pertussis, Tetanus
Conditions
Keywords
Pertussis, Tetanus, Diphtheria, Acellular pertussis, ADACEL®, Tdap vaccine
Brief summary
This study is designed to assess the immunogenicity and safety of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (ADACEL®, Tdap vaccine) as a booster dose in adolescents in Japan. Primary Objective: * To assess the immunogenicity of Tdap (SP306) when administered as a single dose in Japanese adolescents Secondary Objective: * To assess the safety of Tdap vaccine when administered as a single dose in Japanese adolescents.
Detailed description
All participants will receive a single booster dose of Tdap vaccine (ADACEL®) on Day 0 and undergo immunogenicity assessment from blood samples provided prior to, and 28 days post-vaccination. Tolerability and safety will be monitored up to 28 days post-vaccination.
Interventions
BIOLOGICAL(ADACEL®): Tetanus, Reduced Diphtheria Toxoid and Acellular Pertussis
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 11 or 12 years on the day of inclusion * Informed consent form and assent form signed and dated by the parent(s) / legal representative and the subject respectively * Completed childhood vaccination against diphtheria, pertussis and tetanus (i.e, received 4 doses of Japanese-produced tetanus toxoid, diphtheria toxoid and acellular pertussis vaccine absorbed \[DTaP vaccine\]), confirmed by checking immunization records and have not yet undergone additional adsorbed Diphtheria and Tetanus toxoid (DT) vaccination * Able to attend all scheduled visits and to comply with all trial procedures * For female subjects, either pre-menarchal, or post-menarchal with a negative urine pregnancy test.
Exclusion criteria
* Any conditions or diseases which, in the opinion of the investigator * would pose a health risk to the subject * or might interfere with the ability to participate fully in the study * or might interfere with evaluation of the vaccine * or would otherwise make participation inappropriate according to the investigator's clinical judgment * History of diphtheria, tetanus, pertussis, confirmed either clinically, serologically, or microbiologically * Known systemic hypersensitivity to any of the vaccine components or history of a life threatening reaction to a vaccine containing the same substances of the study vaccine * Vaccination in the last 5 years against tetanus, diphtheria, and/or pertussis * Known or suspected congenital immunodeficiency, or current / previous acquired immunodeficiency, or current / previous receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or current / previous (within the last 6 months) systemic corticosteroid therapy * Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial inclusion * Planned participation in another clinical trial during the present trial period * Receipt of blood or blood-derived products in the past 3 months, that might interfere with assessment of the immune response * Receipt of any vaccine within the 4 weeks preceding the trial vaccination, except for influenza vaccination, which may be received at least 2 weeks before the study vaccine * Planned receipt of any vaccine during the trial period * Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or Human Immunodeficiency Virus (HIV) infection * At high risk for diphtheria, tetanus or pertussis infection during the trial * Known pregnancy, or a positive urine pregnancy test * Currently breastfeeding a child * Known thrombocytopenia, contraindicating intramuscular (IM) vaccination, or a history of thrombocytopenia * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination * History of acute disseminated encephalomyelitis, encephalopathy, Guillain-Barré Syndrome (GBS), or autoimmune disease * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily * Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures * Identified as an employee of an Investigator, a study center, a study-affiliated vendor, or the Sponsor, with direct or indirect involvement in the proposed study or other studies under the direction of that Investigator or study center; or identified as a spouse or child (whether natural or adopted) of such an employee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Day 28 post-vaccination | Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.1 IU/mL, post-vaccination. |
| Percentage of Participants With Booster Response to Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Day 28 post-vaccination | Diphtheria booster response was defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.56 IU/mL; or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \> 2.56 IU/mL. Tetanus booster response was defined as a ≥ 4-fold rise in pre- to post- vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.7 IU/mL; or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \> 2.7 IU/mL. |
| Percentage of Participants With Booster Response to Pertussis Antigens, Pertussis Toxoid and Filamentous Hemagglutinin Following Vaccination With ADACEL® | Day 28 post-vaccination | Booster responses were defined as: Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) and a post-vaccination levels ≥ 4x LLOQ; or Pre-vaccination antibody concentrations ≥ LLOQ but \< 4x LLOQ, and a 4-fold rise (i.e., post-/pre-vaccination ≥ 4), or Pre-vaccination antibody concentrations ≥ 4x LLOQ and a 2-fold rise (i.e., post-/pre-vaccination ≥ 2) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL® | Day 0 (pre-vaccination) and Day 28 post-vaccination | — |
| Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Day 0 (pre-vaccination) and Day 28 post-vaccination | — |
| Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination With ADACEL® | Day 0 pre-vaccination | Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.1 IU/mL. |
| Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Day 0 up to Day 7 post-vaccination | Solicited injection-site reactions: Pain, Redness, and Swelling. Grade 3: Pain, Significant, prevents daily activity; Redness and Swelling, \>100 mm. Solicited systemic reactions: Fever (Temperature); Headache, Malaise, and Myalgia. Grade 3: Fever, ≥ 39°C; Headache, Malaise and Myalgia, Significant, prevents daily activity. |
| Percentage of Participants With Booster Response to Pertussis Antigens, Pertactin and Fimbriae Following Vaccination With ADACEL® | Day 28 post-vaccination | Booster responses were defined as: Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) and a post-vaccination levels ≥ 4x LLOQ; or Pre-vaccination antibody concentrations ≥ LLOQ but \< 4x LLOQ, and a 4-fold rise (i.e., post-/pre-vaccination ≥ 4), or Pre-vaccination antibody concentrations ≥ 4x LLOQ and a 2-fold rise (i.e., post-/pre-vaccination ≥ 2) |
| Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL® | Day 0 (pre-vaccination) and day 28 post-vaccination | Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.01 IU/mL. |
| Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL® | Day 0 (pre-vaccination) and day 28 post-vaccination | Seroprotection was defined as the percentage of participants with antibody concentration of ≥1.0 IU/mL. |
Countries
Japan
Participant flow
Recruitment details
The study participants were enrolled from 12 September through 14 October 2012 in 3 clinic centers in Japan.
Pre-assignment details
A total of 43 participants that met all the inclusion criteria but none of the exclusion criteria were enrolled and vaccinated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Study Group Participants received a single booster dose of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis vaccine (Tdap vaccine; ADACEL®) on Day 0. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Categorical <=18 years | 43 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 11.4 Years STANDARD_DEVIATION 0.5 |
| Region of Enrollment Japan | 43 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 43 |
| serious Total, serious adverse events | 0 / 43 |
Outcome results
Primary
Percentage of Participants With Booster Response to Diphtheria and Tetanus Antigens Following Vaccination With ADACEL®
Diphtheria booster response was defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.56 IU/mL; or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \> 2.56 IU/mL. Tetanus booster response was defined as a ≥ 4-fold rise in pre- to post- vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.7 IU/mL; or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \> 2.7 IU/mL.
Time frame: Day 28 post-vaccination
Population: Booster response to diphtheria and tetanus antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Booster Response to Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Diphtheria | 98 Percentage of Participants |
| Study Group | Percentage of Participants With Booster Response to Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Tetanus | 100 Percentage of Participants |
Primary
Percentage of Participants With Booster Response to Pertussis Antigens, Pertussis Toxoid and Filamentous Hemagglutinin Following Vaccination With ADACEL®
Booster responses were defined as: Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) and a post-vaccination levels ≥ 4x LLOQ; or Pre-vaccination antibody concentrations ≥ LLOQ but \< 4x LLOQ, and a 4-fold rise (i.e., post-/pre-vaccination ≥ 4), or Pre-vaccination antibody concentrations ≥ 4x LLOQ and a 2-fold rise (i.e., post-/pre-vaccination ≥ 2)
Time frame: Day 28 post-vaccination
Population: Booster response to pertussis antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Booster Response to Pertussis Antigens, Pertussis Toxoid and Filamentous Hemagglutinin Following Vaccination With ADACEL® | Pertussis toxoid | 63 Percentage of Participants |
| Study Group | Percentage of Participants With Booster Response to Pertussis Antigens, Pertussis Toxoid and Filamentous Hemagglutinin Following Vaccination With ADACEL® | Filamentous hemagglutinin | 88 Percentage of Participants |
Primary
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Following Vaccination With ADACEL®
Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.1 IU/mL, post-vaccination.
Time frame: Day 28 post-vaccination
Population: Seroprotection to diphtheria and tetanus antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Diphtheria | 100 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Following Vaccination With ADACEL® | Tetanus | 100 Percentage of Participants |
Other Pre-specified
Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL®
Time frame: Day 0 (pre-vaccination) and Day 28 post-vaccination
Population: Pre and post vaccination geometric mean concentrations to Diphtheria and Tetanus antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Study Group | Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL® | Diphtheria (Pre-vaccination) | 0.22 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL® | Diphtheria (Post-vaccination) | 8.58 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL® | Tetanus (Pre-vaccination) | 0.46 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Diphtheria and Tetanus Antibodies Pre- and Post-vaccination With ADACEL® | Tetanus (Post-vaccination) | 37.80 Titers |
Other Pre-specified
Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL®
Time frame: Day 0 (pre-vaccination) and Day 28 post-vaccination
Population: Pre and post vaccination geometric mean concentrations to pertussis antibodies were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Fimbriae types 2 and 3 (pre-vaccination) | 7.78 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Pertussis toxoid (pre-vaccination) | 12.21 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Pertussis toxoid (post-vaccination) | 46.92 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Filamentous hemagglutinin (pre-vaccination) | 34.79 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Filamentous hemagglutinin (post-vaccination) | 204.00 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Pertactin (pre-vaccination) | 10.64 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Pertactin (post-vaccination) | 272.82 Titers |
| Study Group | Geometric Mean Concentrations With Respect to Pertussis Antibodies Pre- and Post-vaccination With ADACEL® | Fimbriae types 2 and 3 (post-vaccination) | 748.28 Titers |
Other Pre-specified
Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL®
Solicited injection-site reactions: Pain, Redness, and Swelling. Grade 3: Pain, Significant, prevents daily activity; Redness and Swelling, \>100 mm. Solicited systemic reactions: Fever (Temperature); Headache, Malaise, and Myalgia. Grade 3: Fever, ≥ 39°C; 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) |
|---|---|---|---|
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Solicited injection site Pain | 37 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 solicited injection site Pain | 0 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Solicited injection site Erythema | 9 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 solicited injection site Erythema | 0 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Solicited injection site Swelling | 12 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 solicited injection site Swelling | 1 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Fever | 9 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 Fever | 1 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Headache | 8 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 Headache | 0 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Malaise | 11 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 Malaise | 0 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Myalgia | 17 Participants |
| Study Group | Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With ADACEL® | Grade 3 Myalgia | 0 Participants |
Other Pre-specified
Percentage of Participants With Booster Response to Pertussis Antigens, Pertactin and Fimbriae Following Vaccination With ADACEL®
Booster responses were defined as: Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) and a post-vaccination levels ≥ 4x LLOQ; or Pre-vaccination antibody concentrations ≥ LLOQ but \< 4x LLOQ, and a 4-fold rise (i.e., post-/pre-vaccination ≥ 4), or Pre-vaccination antibody concentrations ≥ 4x LLOQ and a 2-fold rise (i.e., post-/pre-vaccination ≥ 2)
Time frame: Day 28 post-vaccination
Population: Booster response to pertussis antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Booster Response to Pertussis Antigens, Pertactin and Fimbriae Following Vaccination With ADACEL® | Pertactin | 93 Percentage of Participants |
| Study Group | Percentage of Participants With Booster Response to Pertussis Antigens, Pertactin and Fimbriae Following Vaccination With ADACEL® | Fimbriae Types 2 and 3 | 98 Percentage of Participants |
Other Pre-specified
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL®
Seroprotection was defined as the percentage of participants with antibody concentration of ≥1.0 IU/mL.
Time frame: Day 0 (pre-vaccination) and day 28 post-vaccination
Population: Pre- and post-vaccination seroprotection to diphtheria and tetanus antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL® | Diphtheria (Pre-vaccination) | 12 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL® | Diphtheria (Post-vaccination) | 100 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL® | Tetanus (Pre-vaccination) | 30 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination and Post-vaccination With ADACEL® | Tetanus (Post-vaccination) | 100 Percentage of Participants |
Other Pre-specified
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination With ADACEL®
Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.1 IU/mL.
Time frame: Day 0 pre-vaccination
Population: Pre-vaccination seroprotection to diphtheria and tetanus antigens were determined in the Immunology Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination With ADACEL® | Tetanus | 91 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens Pre-vaccination With ADACEL® | Diphtheria | 63 Percentage of Participants |
Other Pre-specified
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL®
Seroprotection was defined as the percentage of participants with antibody concentration of ≥0.01 IU/mL.
Time frame: Day 0 (pre-vaccination) and day 28 post-vaccination
Population: Pre- and post-vaccination seroprotection to diphtheria and tetanus antigens were determined in the Immunology Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL® | Diphtheria (Pre-vaccination) | 100 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL® | Diphtheria (Post-vaccination) | 100 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL® | Tetanus (Pre-vaccination) | 100 Percentage of Participants |
| Study Group | Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Pre-vaccination and Post-vaccination With ADACEL® | Tetanus (Post-vaccination) | 100 Percentage of Participants |