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

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

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.

Study Overview

• Status: Completed
• Conditions: Pertussis; Tetanus; Diphtheria
• Intervention / Treatment: Biological: Tdap (Tetanus Toxoid Reduced Diphtheria Toxoid/Acellular Pertussis); Biological: DTaP (Diphtheria & Tetanus Toxoids & Acellular Pertussis Adsorbed)

• Study Type: Interventional
• Enrollment (Actual): 1045
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
    • Birmingham, Alabama, United States, 35244
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • Fountain Valley, California, United States, 92708
    • Huntington Beach, California, United States, 92647
    • Oakland, California, United States, 94611
    • Roseville, California, United States, 95661
    • Sacramento, California, United States, 95815
  • Connecticut
    • Norwich, Connecticut, United States, 06360
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
    • Crestview Hills, Kentucky, United States, 41017
    • Louisville, Kentucky, United States, 40291
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
  • Maryland
    • Frederick, Maryland, United States, 21702
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
    • Omaha, Nebraska, United States, 68131
    • Omaha, Nebraska, United States, 68124
    • Omaha, Nebraska, United States, 68132
  • New York
    • Rochester, New York, United States, 14618
  • North Dakota
    • Fargo, North Dakota, United States, 58103
  • Ohio
    • Cleveland, Ohio, United States, 44121
  • Oregon
    • Gresham, Oregon, United States, 97030
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
    • Norristown, Pennsylvania, United States, 19401
    • Pittsburgh, Pennsylvania, United States, 15236
    • Pittsburgh, Pennsylvania, United States, 15241
    • Rydal, Pennsylvania, United States, 19046
    • Uniontown, Pennsylvania, United States, 15401
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
    • Tullahoma, Tennessee, United States, 37388
  • Texas
    • San Antonio, Texas, United States, 78229
  • Utah
    • Layton, Utah, United States, 84041
    • Springville, Utah, United States, 84663
  • Virginia
    • Chesapeake, Virginia, United States, 23321
    • Midlothian, Virginia, United States, 23113
  • Washington
    • Spokane, Washington, United States, 99202
    • Spokane, Washington, United States, 99218
  • Wisconsin
    • LaCrosse, Wisconsin, United States, 54601

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; DAPTACEL primed participants	Biological: Tdap (Tetanus Toxoid Reduced Diphtheria Toxoid/Acellular Pertussis); 0.5 mL, IM; Other Names: Adacel
Experimental: Group 2; Pentacel primed participants	Biological: DTaP (Diphtheria & Tetanus Toxoids & Acellular Pertussis Adsorbed); 0.5 mL, IM; Other Names: DAPTACEL in the US; TRIPACEL in Canada

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting at Least 1 Solicited Injection Site or Solicited Systemic Reaction Post-vaccination	Solicited Injection Site Reactions: Pain, erythema/redness, swelling, increased left limb circumference, and increased right limb circumference. Solicited Systemic Reactions: Fever (temperature), headache, malaise, and myalgia.	Days 0 to 7 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: April 27, 2007
• First Submitted That Met QC Criteria: April 27, 2007
• First Posted (Estimate): April 30, 2007

Study Record Updates

• Last Update Posted (Estimate): February 7, 2014
• Last Update Submitted That Met QC Criteria: January 10, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Tetanus; Diphtheria; Pertussis; ADACEL; DAPTACEL
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Clostridium Infections; Corynebacterium Infections; Whooping Cough; Tetanus; Diphtheria
• Other Study ID Numbers: TD517