Diphtheria, Pertussis, Poliomyelitis, Tetanus
Conditions
Keywords
Diphtheria, Tetanus, Pertussis, Poliomyelitis
Brief summary
The present study is designed to meet the requirements of the Taiwanese Health Authorities for registration of ADACEL POLIO in Taiwan. Subjects will receive one dose of the study vaccine at 6 to 8 years of age. Blood samples will be taken for antibody titration. The expected total duration of follow-up for each subject will be 28 days.
Interventions
BIOLOGICALTdcP-IPV vaccine
0.5 mL, Intramuscular
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 8 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 6 to 8 years on the day of inclusion * Informed consent form signed by the parent(s) or another legally acceptable representative * Subject and parent/guardian able to attend all scheduled visits and comply with all trial procedures * Written documentation of complete primary series and fourth dose of diphtheria, tetanus, pertussis (DTP) and Polio vaccines * Parent(s)/legal representative present or fully completed pre-inclusion medical questionnaire.
Exclusion criteria
* Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the trial vaccination * Planned participation in another clinical trial during the present trial period * Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy * Known systemic hypersensitivity to any of the vaccine components (or residues carried over from manufacture, such as formaldehyde, glutaraldehyde, streptomycin, neomycin and polymyxin B ) or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances with specific focus on subjects who had, after previous administration of DTP vaccine, one of the pre-listed adverse events. * Chronic illness, at a stage that could interfere with trial conduct or completion, in the opinion of the investigator * Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, progressive encephalopathy * Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of immune response * Receipt of any vaccine in the 4 weeks preceding the trial vaccination * Planned receipt of any vaccine in the 4 weeks following the trial vaccination * Known Human Immunodeficiency Virus (HIV), Hepatitis B surface (HBs) antigen, or Hepatitis C seropositivity * History of diphtheria and/or tetanus and/or pertussis and/or poliomyelitis infection (confirmed either clinically, serologically or microbiologically) * Previous fifth vaccination against diphtheria and/or tetanus and/or pertussis and/or poliomyelitis diseases with either the trial vaccine or another vaccine * Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular (IM) vaccination * Subject at high risk for diphtheria and/or tetanus and/or pertussis and/or poliomyelitis infection during the trial * Received oral or injected antibiotic therapy within the 72 hours prior to any blood draw * Febrile illness (temperature ≥ 37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to investigator judgment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Day 28 post-vaccination | Diphtheria concentrations determined by diphtheria toxin neutralization assay (Dip SN); Tetanus concentrations determined by enzyme-linked immunosorbent assay (ELISA). Seroprotection titer levels were defined as: Anti-diphtheria antibody titers ≥0.1 international unit (IU) per milliliter (mL); Anti-tetanus antibody titers ≥0.01 IU/mL and ≥0.1 IU/mL; Anti-Polio (≥ 8 1/dilution). |
| Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Day 28 post-vaccination | The anti-Pertussis concentration were determined by ELISA. The criteria for demonstrating booster response are: (i) Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) for each anti-pertussis antibody (PT, FHA, FIM, and PRN) but a post-vaccination levels ≥ 4 x LLOQ; or (ii) Pre-vaccination antibody concentrations ≥ LLOQ but \< 4 x LLOQ with a 4-fold rise rate; or (iii) Pre-vaccination antibody concentrations ≥ 4 x LLOQ but with a 2-fold rise rate. |
| Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Day 28 post-vaccination | Diphtheria antibody concentrations determined by diphtheria toxin neutralization assay; Tetanus antibody concentrations determined by enzyme-linked immunosorbent assay (ELISA). |
| Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Day 0 (pre-vaccination) and Day 28 post-vaccination | Pre- and post-vaccination GMTs for the Pertussis toxoid (PT), Pertussis filamentous hemagglutinin (FHA), Pertussis pertactin (PRN), and Pertussis Fimbriae types 2 and 3 (FIM), all determined by enzyme-linked immunosorbent assay (ELISA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Day 0 up to Day 7 post-vaccination | Solicited Injection Site Reactions: Pain, Erythema/redness, Swelling, and Extensive swelling of vaccinated limb. Solicited Systemic Reactions: Fever (temperature ≥ 37.5ºC), Headache, Malaise, and Myalgia. |
Countries
Taiwan
Participant flow
Recruitment details
Participants were enrolled from 24 November 2008 to 11 March 2009 at 1 medical center in Taiwan.
Pre-assignment details
A total of 132 participants who met the inclusion and none of the exclusion criteria were enrolled, vaccinated, and evaluated.
Participants by arm
| Arm | Count |
|---|---|
| ADACEL POLIO Vaccine Study Group Participants received one dose of Tetanus, diphtheria (reduced antigen content), pertussis (acellular components) vaccine (TdcP-IPV, ADACEL Polio) on Day 0 | 132 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | ADACEL POLIO Vaccine Study Group |
|---|---|
| Age, Categorical <=18 years | 132 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 6.89 Years STANDARD_DEVIATION 0.3 |
| Region of Enrollment Taiwan | 132 participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 102 / 132 |
| serious Total, serious adverse events | 2 / 132 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination
Diphtheria antibody concentrations determined by diphtheria toxin neutralization assay; Tetanus antibody concentrations determined by enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 28 post-vaccination
Population: Geometric mean titers were assessed in the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Anti-Polio 2 (Post-vaccination) | 7083 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Anti-Polio 3 (Post-vaccination) | 9860 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Anti-Diphtheria (Post-vaccination) | 3.81 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Anti-Tetanus (Post-vaccination) | 17.2 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers (GMTs) of Antibodies to ADACEL Polio Vaccine Antigens Following Vaccination | Anti-Polio 1 (Post-vaccination) | 9627 Titers |
Primary
Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio
Pre- and post-vaccination GMTs for the Pertussis toxoid (PT), Pertussis filamentous hemagglutinin (FHA), Pertussis pertactin (PRN), and Pertussis Fimbriae types 2 and 3 (FIM), all determined by enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 0 (pre-vaccination) and Day 28 post-vaccination
Population: Geometric mean titers to the vaccine Pertussis antigens were assessed in the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Pertussis Toxoid (Pre-vaccination) | 4.53 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Pertussis Toxoid (Post-vaccination) | 42.7 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Filamentous hemagglutinin (Pre-vaccination) | 19.7 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Filamentous hemagglutinin (Post-vaccination) | 164 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Fimbriae types 2 and 3 (Pre-vaccination) | 17.5 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Fimbriae types 2 and 3 (Post-vaccination) | 423 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Pertactin (Pre-vaccination) | 11.9 Titers |
| ADACEL POLIO Vaccine Study Group | Geometric Mean Titers of Antibodies to Pertussis Antigens Following Vaccination With ADACEL Polio | Anti-Pertactin (Post-vaccination) | 314 Titers |
Primary
Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine.
The anti-Pertussis concentration were determined by ELISA. The criteria for demonstrating booster response are: (i) Pre-vaccination antibody concentrations less than the lower limit of quantitation (LLOQ) for each anti-pertussis antibody (PT, FHA, FIM, and PRN) but a post-vaccination levels ≥ 4 x LLOQ; or (ii) Pre-vaccination antibody concentrations ≥ LLOQ but \< 4 x LLOQ with a 4-fold rise rate; or (iii) Pre-vaccination antibody concentrations ≥ 4 x LLOQ but with a 2-fold rise rate.
Time frame: Day 28 post-vaccination
Population: Anti-Pertussis concentrations were assessed in the per-protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ADACEL POLIO Vaccine Study Group | Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Pertussis (N = 114) | 88 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Filamentous Hemagglutinin (N = 130) | 126 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Fimbriae types 2 and 3 (N = 130) | 116 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Booster Response to Vaccine Pertussis Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Pertactin (N = 131) | 130 Participants |
Primary
Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine.
Diphtheria concentrations determined by diphtheria toxin neutralization assay (Dip SN); Tetanus concentrations determined by enzyme-linked immunosorbent assay (ELISA). Seroprotection titer levels were defined as: Anti-diphtheria antibody titers ≥0.1 international unit (IU) per milliliter (mL); Anti-tetanus antibody titers ≥0.01 IU/mL and ≥0.1 IU/mL; Anti-Polio (≥ 8 1/dilution).
Time frame: Day 28 post-vaccination
Population: Anti-tetanus and anti-diphtheria concentrations were assessed in the per-protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ADACEL POLIO Vaccine Study Group | Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Diphtheria (Post-vaccination) | 131 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Tetanus (Post-vaccination) | 131 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Polio 1 (Post-vaccination) | 131 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Polio 2 (Post-vaccination) | 131 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants With Seroprotection to Vaccine Antigens Following Vaccination With ADACEL Polio (TdcP-IPV) Vaccine. | Anti-Polio 3 (Post-vaccination) | 131 Participants |
Secondary
Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine
Solicited Injection Site Reactions: Pain, Erythema/redness, Swelling, and Extensive swelling of vaccinated limb. Solicited Systemic Reactions: Fever (temperature ≥ 37.5ºC), Headache, Malaise, and Myalgia.
Time frame: Day 0 up to Day 7 post-vaccination
Population: Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Injection site Erythema (N = 129) | 61 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Erythema (≥5 cm; N = 129) | 4 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Headache (N = 130) | 28 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Headache (Prevents daily activities; N=130 | 1 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Myalgia (N = 130) | 46 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Solicited Injection Site Reaction | 112 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Injection site Swelling (N = 129) | 40 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Swelling (≥5 cm; N = 129) | 2 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any injection site Pain (N = 129) | 102 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Pain (Incapacitating; N = 129) | 1 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any extensive swelling of vaccinated limb (N=129) | 0 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 extensive swelling of vaccinated limb N129 | 0 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Solicited Systemic Reaction (N = 130) | 63 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Fever (N = 130) | 14 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Fever (> 39.0°C; N = 130) | 2 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Myalgia (Prevents daily activities; N=130) | 0 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Any Malaise (N = 130) | 27 Participants |
| ADACEL POLIO Vaccine Study Group | Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With ADACEL Polio Vaccine | Grade 3 Malaise (Prevents daily activities; N=130) | 0 Participants |