Immunogenicity and Safety of Boostrix Polio Vaccine as a Booster Dose in 5 to 6-year-old Children.

Study Overview
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Brief Summary
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This phase 3b study will compare the immunogenicity and reactogenicity of the dTpa-IPV vaccine to that of a DTPa-IPV vaccine when administered as a booster dose in healthy children 5-6 years of age who have received three primary vaccination doses of DTPa-based vaccine according to the 3-5-11 month schedule recommended in Italy. In this study, MMRV vaccine will also be co-administered to all children.

Official Title
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Immunogenicity and Safety of GSK Biologicals' dTpa-IPV Vaccine (Boostrix Polio) as a Booster Dose in 5 to 6-year-old Children.

Conditions
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Acellular Pertussis, Tetanus, Diphtheria, Poliomyelitis

Intervention / Treatment
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* Biological: Boostrix Polio™ 711866
* Biological: Priorix Tetra TM 208136
* Biological: Tetravac TM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female child of 5 and 6 years of age at the time of vaccination. Subjects who received a complete 3-dose vaccination with a DTPa-based combined vaccine according to a 3-5-11 month schedule in line with recommendations in Italy. Subjects who received a first dose of a live attenuated measles-mumps-rubella vaccine in the second year of life, in line with recommendations in Italy. Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. Previous booster vaccination against tetanus, diphtheria, pertussis and/or poliomyelitis since vaccination in the first two years of life. Previous measles, mumps, rubella and/or varicella second dose vaccination. Known history of diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella and/or varicella disease. Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to study start. Any confirmed or suspected immunosuppressive or immunodeficiency condition, based on medical history and physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Administration of immunoglobulin and/or any blood products within the three months preceding vaccination or planned administration during the study period. Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus. Occurrence of any of the following adverse events after a previous administration of a DTP vaccine: Hypersensitivity reaction to any component of the vaccine; Encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis-containing vaccine; Fever >= 40°C within 48 hours of vaccination, not due to another identifiable cause; Collapse or shock-like state within 48 hours of vaccination; Convulsions with or without fever, occurring within 3 days of vaccination. Residence in the same household as a person high risk for varicella The following condition is temporary or self-limiting, and a subject may be vaccinated once the condition has resolved if no other exclusion criteria is met: Current febrile illness or axillary temperature ≥ 38.5 ºC or other moderate to severe illness within 24 hours of study vaccine administration.

Ages Eligible for Study
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Minimum Age: 5 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOOSTRIX POLIO GROUP<br>Healthy male or female children, between and including 5 to 6 years of age, who were primed with three doses of Infanrix™ vaccine according to the Italian 3-5-11 month vaccination schedule, additionally received a single booster dose of Boostrix Polio™ vaccine co-administered with a single dose of Priorix Tetra™ vaccine at Day 0. Boostrix Polio™ vaccine was administered intramuscularly in the deltoid region of the left upper arm, while the Priorix Tetra™ vaccine was administered subcutaneously in the deltoid region of the right upper arm. | Biological: Boostrix Polio™ 711866<br>* Single dose, intramuscular administration.<br>* Other names: dTpa-IPV;Biological: Priorix Tetra TM 208136<br>* Single dose, subcutaneously.<br>* Other names: MMRV;|
| Active Comparator: TETRAVAC GROUP<br>Healthy male or female children, between and including 5 to 6 years of age, who were primed with three doses of Infanrix™ vaccine according to the Italian 3-5-11 month vaccination schedule, additionally received a single booster dose of Tetravac™ vaccine co-administered with a single dose of Priorix Tetra™ vaccine at Day 0. Tetravac™ vaccine was administered intramuscularly in the deltoid region of the left upper arm, while the Priorix Tetra™ vaccine was administered subcutaneously in the deltoid region of the right upper arm. | Biological: Priorix Tetra TM 208136<br>* Single dose, subcutaneously.<br>* Other names: MMRV;Biological: Tetravac TM<br>* Single dose, intramuscular administration.<br>* Other names: DTPa-IPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). The reference cut-off value was greater than or equal to (≥) 0.1 IU/mL. | At Month 1, one month post-vaccination | 
| Anti-poliovirus Types 1, 2 and 3 Antibody Titres | Antibody titers were presented as geometric mean titers (GMTs) for the assay cut-off ≥ the value of 8. | At Month 1, one month post-vaccination | 
| Number of Seroprotected Subjects Against Polio Types 1, 2 and 3 | A seroprotected subject was defined as a subject with anti-polio types 1, 2 and 3 titers ≥ the value of 8. Antibody titers have been assessed by neutralization assay. | At Month 1, one month post-vaccination | 
| Number of Seropositive Subjects for Anti-D and Anti-T Antibodies | A seropositive subject was defined as a subject with anti-D and anti-T concentrations ≥ 0.1 IU/mL. Antibody concentrations have been assessed by enzyme-linked immunosorbent assay (ELISA). | At Month 1, one month post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens | A seroprotected subject was defined as a subject with anti-D and anti-T concentrations ≥ 1.0 IU/mL. Antibody concentrations have been assessed by ELISA. | At Month 1, one month post-vaccination | 
| Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations, expressed in ELISA units per milliliter (EL.U/mL). The reference cut-off value was ≥ 5 EL.U/mL. | At Month 1, one month post-vaccination | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | A seropositive subject was defined as a subject with anti-PT, anti-FHA and anti-PRN concentrations ≥ 5.0 IU/mL. Antibody concentrations have been assessed by ELISA. | At Month 1, one month post-vaccination | 
| Number of Seropositive Subjects for Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella | Seropositivity was defined as: subjects with antibody concentrations ≥ 150 milli-international units per milliliter (mIU/mL), ≥ 231 units per milliliter (U/mL), ≥ 4 international units per milliliter (IU/mL) and ≥ 50 mIU/mL for anti-measles, anti-mumps, anti-rubella and anti-varicella antibodies, respectively. | At Month 1, one month post-vaccination | 
| Anti-measles and Anti-varicella Antibody Concentrations | Antibody concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in mIU/mL. | At Month 1, one month post-vaccination | 
| Anti-mumps Antibody Concentrations | Antibody concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in U/mL. | At Month 1, one month post-vaccination | 
| Anti-rubella Antibody Concentrations | Antibody concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in IU/mL. | At Month 1, one month post-vaccination | 
| Number of Subjects With Booster Responses to Anti-D and Anti-T | Booster responses to anti-D and anti-T were defined as: For initially seronegative subjects (pre-vaccination concentration < cut-off of 0.1 IU/mL), antibody concentrations at least four times the assay cut-off (post-vaccination concentration ≥ 0.4 IU/mL). For initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL), an increase in antibody concentrations of at least four times the pre-vaccination concentration. | At Month 1, one month post-vaccination | 
| Number of Subjects With Booster Responses to Anti-polio Type 1, 2 and 3 | Booster response to the poliovirus antigens was defined as: For initially seronegative subjects (pre-vaccination antibody titre < cut-off of 8), antibody titre ≥ 32. For initially seropositive subjects (pre-vaccination antibody titres ≥ 8), an increase in antibody titres of at least four times the pre-vaccination titre. | At Month 1, one month post-vaccination | 
| Number of Subjects With Booster Responses to Anti-PT, Anti-FHA and Anti-PRN | Booster response to the PT, FHA and PRN antigens was defined as: For initially seronegative subjects (pre-vaccination concentration < cut-off of 5 EL.U/mL), antibody concentrations at least four times the cut-off (post-vaccination concentration ≥ 20 EL.U/mL). For initially seropositive subjects with pre-vaccination concentration ≥ 5 EL.U/mL and < 20 EL.U/mL, an increase in antibody concentrations of at least four times the pre-vaccination concentration. For initially seropositive subjects with pre-vaccination concentration ≥ 20 EL.U/mL, an increase in antibody concentrations of at least two times the pre-vaccination concentration. | At Month 1, one month post-vaccination | 
| Number of Seroconverted Subjects for Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella | Seroconversion for anti-measles, anti-mumps, anti-rubella and anti-varicella was defined as the appearance of antibodies after vaccination in subjects who were seronegative before vaccination. There were no seronegative subjects for anti-rubella antibodies, prior to vaccination. | At Month 1, one month post-vaccination | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) post-vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the whole study period (from Month 0 to Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Boostrix Polio, dTpa-IPV