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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Tetanus, Diphtheria, Pertussis, Measles, Polio

Intervention / Treatment
-----------------
* 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
* 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


Participation Criteria
=================
Eligibility 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.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1<br>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<br>* 0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)<br>* Other names: VARIVAX®;|
| Experimental: Study Group 2<br>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<br>* 0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®<br>* Other names: VARIVAX®;|
| Experimental: Study Group 3<br>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<br>* 0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)<br>* Other names: VARIVAX®;|
| Experimental: Study Group 4<br>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<br>* 0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®<br>* Other names: VARIVAX®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Booster Response to the Pertussis Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | 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. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Concentrations of the Pertussis Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | 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). | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants With Booster Response to Tetanus and Diphtheria Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | 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. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Concentrations of the Tetanus and Diphtheria Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | Geometric mean concentrations to anti-tetanus and anti-diphtheria were measured by enzyme-linked immunosorbent assay (ELISA). | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants With Booster Response to Polio Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | 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. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Concentrations of Polio Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine | Geometric mean concentrations to anti-polio were measured by enzyme-linked immunosorbent assay (ELISA). | Day 0 (pre-vaccination) and Day 28 post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DAPTACEL®, VARIVAX®, Tetanus, Diphtheria, Pertussis, DTap-IPV