Study of DTap-IPV Compared to DAPTACEL® and IPOL® as the 5th Dose in Children 4 to 6 Years of Age

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01346293
First received: April 29, 2011
Last updated: May 28, 2015
Last verified: May 2015
  Purpose

The study was designed to compare the safety and immunogenicity of DTap-IPV with DAPTACEL® + IPOL® as the 5th dose booster in children ≥ 4 to < 7 years of age in the US and Puerto Rico who were previously vaccinated with DAPTACEL® and/or Pentacel® vaccines only.

Primary Objectives:

  • To compare the pertussis [Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN), and Fimbriae Types 2 and 3 (FIM)] booster responses and geometric mean concentrations (GMCs) (as measured by enzyme-linked immunosorbent assay [ELISA]) following DTap-IPV vaccination to those elicited following DAPTACEL® + IPOL® vaccination when administered as a 5th dose.
  • To compare the diphtheria and tetanus booster responses and GMCs (as measured by ELISA) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations when administered as a 5th dose .
  • To compare the Inactivated Poliovirus Vaccine booster responses (as measured by neutralizing assay) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations.

Observational Objectives:

  • To compare the polio (types 1, 2, and 3) geometric mean titers (GMTs) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations.
  • To assess the safety of DTap-IPV vaccine or DAPTACEL® + IPOL® vaccine when administered as the fifth dose booster vaccine in participants previously vaccinated with DAPTACEL and/or Pentacel vaccines.

Condition Intervention Phase
Tetanus
Diphtheria
Pertussis
Measles
Polio
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity of DTap-IPV (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined With Inactivated Poliovirus Vaccine) Compared to DAPTACEL® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) + IPOL® (Poliovirus Vaccine Inactivated) as the 5th Dose in Children 4 to 6 Years of Age

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Participants With Booster Response to the Pertussis Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Booster responses to pertussis antigens [pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM)] were measured by enzyme-linked immunosorbent assay (ELISA). Booster responses were defined as participants with either a pre-vaccination antibody concentration less than lower limit of quantitation (<LLOQ), achieving a post-vaccination level ≥4X LLOQ, or pre-vaccination antibody concentrations ≥LLOQ but <4X LLOQ, achieving a 4-fold rise rate of post-vaccination, or a pre-vaccination antibody concentration ≥4X LLOQ, achieving a 2-fold response.

  • Geometric Mean Concentrations of the Pertussis Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Geometric mean concentrations to pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae types 2 and 3 [FIM]) were measured by enzyme-linked immunosorbent assay (ELISA).

  • Number of Participants With Booster Response to Tetanus and Diphtheria Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Anti-Diphtheria antibodies were measured by a toxin neutralization test. Booster responses were defined as participants with a pre-vaccination antibody concentration <0.1 IU/ml, achieving a post-vaccination level ≥0.4 IU/ml, or a pre-vaccination antibody concentration ≥0.1 IU/ml but <2.0 IU/ml, achieving a 4-fold rise rate post-vaccination, or a pre-vaccination antibody concentration ≥2.0 IU/ml, achieving a 2-fold response.

  • Geometric Mean Concentrations of the Tetanus and Diphtheria Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Geometric mean concentrations to anti-tetanus and anti-diphtheria were measured by enzyme-linked immunosorbent assay (ELISA).

  • Number of Participants With Booster Response to Polio Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Anti-poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Booster responses were defined as participants with a pre-vaccination antibody concentration <1:8 dil, achieving a post-vaccination level ≥1:8 dil, or a pre-vaccination antibody concentration ≥1:8 dil, achieving a 4-fold response.

  • Geometric Mean Concentrations of Polio Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Geometric mean concentrations to anti-polio were measured by enzyme-linked immunosorbent assay (ELISA).


Other Outcome Measures:
  • Number of Participants With Seroprotection Against the Tetanus and Diphtheria Antigens Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Anti-Tetanus antibodies were measured by ELISA. Anti diphtheria antibodies were measured by a toxin neutralization test. Seroprotection for anti-tetanus and anti-diphtheria was defined as antibody concentrations ≥0.1 IU/ml and ≥1.0 IU/ml.

  • Number of Participants With Seroprotection Against the Polio Antigens Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Seroprotection for anti-polio types was defined as antibody titers ≥1:8 dilution.

  • Number of Participants With Booster Response to the Polio Antigens Following Vaccination With Inactivated Poliovirus (IPV) Vaccine as a 4th or 5th Dose [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ] [ Designated as safety issue: No ]
    Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Four-fold rise in booster responses between groups was defined as post/pre-vaccination ≥4.

  • Summary of Anti-Polio Geometric Mean Titers in Participants That Received Inactivated Poliovirus (IPV) Vaccine as a 4th and 5th Dose [ Time Frame: Day 0 (pre-booster vaccination) and Day 28 post-booster vaccination ] [ Designated as safety issue: No ]
    Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay.

  • Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine [ Time Frame: Day 0 up to Day 28 post-final vaccination ] [ Designated as safety issue: No ]
    Solicited injection-site: Pain, Erythema, Swelling, Extensive Swelling of Vaccinated Limb, Change in Limb Circumference. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 injection-site: Pain, Incapacitating, unable to perform usual activities; Erythema, Swelling, ≥50 mm; Change in limb circumference >50 mm increase over pre-vaccination measurement; Extensive limb swelling (ELS) was considered severe. Grade 3 systemic reactions: Fever ≥39.0˚C; Headache, Malaise, and Myalgia Significant, prevents daily activity.


Enrollment: 3372
Study Start Date: April 2011
Study Completion Date: September 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Group 1
Participants will receive concomitantly a dose of DTap-IPV, a dose of M-M-R®II, and a dose of VARIVAX® vaccine on Day 0
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus
0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)
Other Names:
  • DTap-IPV
  • M-M-R®II
  • VARIVAX®
Experimental: Study Group 2
Participants will receive concomitantly a dose of DAPTACEL®, a dose of IPOL®, a dose of M-M-R®II, and a dose of VARIVAX® vaccines on Day 0
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus
0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®
Other Names:
  • DAPTACEL®
  • IPOL®
  • M-M-M R®II
  • VARIVAX®
Experimental: Study Group 3
Participants will receive concomitantly a dose of DTap-IPV with or without a dose of M-M-R®II and a dose of VARIVAX® on Day 0
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus
0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)
Other Names:
  • DTap-IPV
  • M-M-R®II
  • VARIVAX®
Experimental: Study Group 4
Participants will receive concomitantly a dose of DAPTACEL® vaccine, a dose of IPOL® vaccine with or without a dose of M-M-R®II and a dose of VARIVAX® vaccines on Day 0
Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus
0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®
Other Names:
  • DAPTACEL®
  • IPOL®
  • M-M-R®II
  • VARIVAX®

Detailed Description:

All participants will be randomized to receive either one dose each of DTap-IPV + Measles, Mumps, and Rubella Virus Vaccine Live (M-M-R®II) + VARIVAX® or one dose each of DAPTACEL® + IPOL® + M-M-R®II + VARIVAX® on Day 0.

  Eligibility

Ages Eligible for Study:   4 Years to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged ≥ 4 to < 7 years on the day of inclusion
  • Informed consent form has been signed and dated by the parent/guardian before the first study-related procedure
  • Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures
  • Subject has documented completion of primary infant series and booster with DAPTACEL® and/or Pentacel® vaccine(s) only.

Exclusion Criteria:

  • Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial vaccination
  • Planned participation in another clinical trial during the present trial period
  • Receipt of any vaccine in the 4 weeks preceding the trial vaccination, except for any influenza vaccine, which may be received at least 2 weeks before study vaccines
  • Planned receipt of any vaccine in the 4 weeks following the trial vaccination except for any influenza vaccine, which may be received at least 2 weeks after study vaccines
  • Receipt of blood or blood-derived products in the past 3 months
  • 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)
  • History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • History of diphtheria, tetanus, or pertussis infection, confirmed either clinically, serologically, or microbiologically
  • Known systemic hypersensitivity to any of the vaccines' components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
  • Laboratory-confirmed thrombocytopenia, contraindicating intramuscular vaccination
  • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
  • Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
  • Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01346293

  Show 72 Study Locations
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01346293     History of Changes
Other Study ID Numbers: M5I02, U1111-1116-4842
Study First Received: April 29, 2011
Results First Received: April 23, 2015
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Tetanus
Diphtheria
Pertussis
DTap-IPV
DAPTACEL®
VARIVAX®

Additional relevant MeSH terms:
Diphtheria
Tetanus
Whooping Cough
Actinomycetales Infections
Bacterial Infections
Bordetella Infections
Clostridium Infections
Corynebacterium Infections
Gram-Negative Bacterial Infections
Gram-Positive Bacterial Infections
Infection
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on August 03, 2015