Safety and Immunogenicity of Tdap Vaccine Compared to DTaP Vaccine in Children 4 to 6 Years of Age

Study Overview
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Brief Summary
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Currently, there is no 5-component acellular pertussis vaccine licensed for the 5th dose in US children aged 4 to 6 years.This study is aimed at providing evidence of sero-protection, booster response and safety of this formulation as a 5th dose. Primary Objective: - To compare the immune responses of Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) Vaccine to Diphtheria, tetanus and acellular pertussis (DTaP) vaccine (all antigens) when each is administered as a 5th dose and given concurrently, to children aged 4 to 6 years. Secondary/Observational Objectives: To compare the immune responses for pertussis antigens of Tdap Vaccine to DTaP vaccine (for pertussis antigens) when each is administered as a 5th dose and given concurrently, to children aged 4 to 6 years. To present the long-term immunogenicity at 1-, 3-, and 5-years post-vaccination after each long-term follow-up. To describe the safety profile following vaccine administration.

Official Title
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Safety and Immunogenicity of Tdap Vaccine Compared to DTaP Vaccine as Fifth Dose Booster in Children 4 to 6 Years of Age

Conditions
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Tetanus, Diphtheria, Pertussis

Intervention / Treatment
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* Biological: Tdap (Tetanus Toxoid Reduced Diphtheria Toxoid/Acellular Pertussis)
* Biological: DTaP (Diphtheria & Tetanus Toxoids & Acellular Pertussis Adsorbed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Healthy, as determined by medical history and physical examination. Aged 4 to 6 (< 7) years at the time of study vaccination on Day 0. Signed and dated informed consent form that has been approved by the Institutional Review Board (IRB) by the parent or legally authorized representative. Signed and dated informed assent form from the subject if required by the IRB. Able to attend scheduled visits at Visit 1 and Visit 2 and able to comply with all trial procedures. Subjects will be invited to participate in the long-term immunogenicity follow-up study but a commitment to participate in the long-term is not required as an inclusion criterion. Documented vaccination history of 4 previous doses of DAPTACEL according to the recommended national immunization schedule for Diphtheria, tetanus and acellular pertussis (DTaP). Exclusion Criteria : Participation in another clinical trial in the 4 weeks preceding the trial vaccination. Planned participation in another clinical trial during the original trial period. 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. Systemic hypersensitivity to any of the vaccine components or history of life-threatening reaction to the trial vaccine or a vaccine containing the same substances. Chronic illness at a stage that could interfere with trial conduct or completion. Blood or blood-derived products received in the past 3 months. Receipt of any other vaccine within 30 days prior to study vaccination, or planning to receive another vaccine within 30 days before the Visit 2 blood draw (with the exception of the annual influenza vaccine). History of diphtheria, tetanus or pertussis infection (confirmed either serologically or microbiologically). Thrombocytopenia or bleeding disorder contraindicating intra muscular vaccination.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>DAPTACEL primed participants | Biological: Tdap (Tetanus Toxoid Reduced Diphtheria Toxoid/Acellular Pertussis)<br>* 0.5 mL, IM<br>* Other names: Adacel;|
| Experimental: Group 2<br>Pentacel primed participants | Biological: DTaP (Diphtheria & Tetanus Toxoids & Acellular Pertussis Adsorbed)<br>* 0.5 mL, IM<br>* Other names: TRIPACEL in Canada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Seroprotection at Baseline and 30 Days Post-vaccination for Diphtheria and Tetanus at ≥ 0.1 IU/mL Level | Seroprotection rate at level ≥ 0.1 IU/mL was defined as antibody concentrations ≥ 0.1 IU/mL. Diphtheria titers were determined by toxin neutralization assay; tetanus titers were determined by enzyme-linked immunosorbent assay (ELISA). | Pre-dose and 30 days post-vaccination | 
| Percentage of Participants Who Achieved Serothreshold at Baseline and 30 Days Post-vaccination for Diphtheria and Tetanus at Level ≥ 1.0 IU/mL | Serothreshold rate at level ≥ 1.0 IU/mL was defined as antibody concentrations ≥ 1.0 IU/mL. Diphtheria titers were determined by toxin neutralization assay; tetanus titers were determined by enzyme-linked immunosorbent assay (ELISA). | Pre-dose and 30 days post-vaccination | 
| Percentage of Participants Who Demonstrated Booster Response at 30 Days Post-Vaccination for Pertussis | Booster response was defined as post titer ≥ 0.4 IU/mL and pre-titer < 0.1 IU/mL, or Post/Pre titer ≥ 4 increase and pre titer ≥ 0.1 IU/mL but < 2 IU/mL, or Post/Pre titer ≥ 2 increase and pre-titer ≥ 2 IU/mL Post-vaccination titers for pertussis toxoid (PT), pertussis filamentous hemagglutinin (FHA), pertussis pertactin (PRN), and pertussis Fimbriae types 2 and 3 (FIM), were determined by enzyme-linked immunosorbent assay (ELISA). | 30 Days post-vaccination | 
| Percentage of Participants Who Demonstrated Booster Response at 30 Days Post-Vaccination for Diphtheria and Tetanus | Booster response was defined as post titer ≥ 0.4 IU/mL and pre titer < 0.1 IU/mL, or Post/Pre titer ≥ 4 increase and pre-titer ≥ 0.1 IU/mL but < 2 IU/mL, or Post/Pre titer ≥ 2 increase and pre-titer ≥ 2 IU/mL. Post-vaccination titers for Diphtheria was determined by neutralization assay; tetanus titers was determined by an enzyme-linked immunosorbent assay (ELISA). | 30 Days post-vaccination | 
| Geometric Mean Titers (GMTs) at Baseline and 30 Days Post Vaccination for Pertussis | Pre- and post-vaccination GMTs and their 95% confidence intervals for pertussis toxoid (PT), pertussis filamentous hemagglutinin (FHA), pertussis pertactin (PRN), and pertussis Fimbriae types 2 and 3 (FIM), were determined by enzyme-linked immunosorbent assay (ELISA). | Pre-dose and 30 Days Post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tetanus; Diphtheria; Pertussis; ADACEL; DAPTACEL