Immunogenicity and Safety of GSK Biologicals' Boostrix Polio Vaccine in 3 and 4-year-old Children

Study Overview
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Brief Summary
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The purpose of the study is to compare the immunogenicity and safety of a booster dose of BoostrixTM Polio to that of Sanofi Pasteur MSD's RepevaxTM, when co-administered with a second dose of PriorixTM, in healthy 3 and 4-year-old children.

Official Title
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Immunogenicity and Safety of GSK Biologicals' dTpa-IPV Vaccine (Boostrix Polio) as a Booster Dose in 3 and 4-year-old Children

Conditions
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Acellular Pertussis, Poliomyelitis, Tetanus, Diphtheria

Intervention / Treatment
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* Biological: Boostrix PolioTM
* Biological: RepevaxTM
* Biological: PriorixTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol should be enrolled in the study. A male or female child of 3 or 4 years of age at the time of booster vaccination (up to, but excluding 5 years of age). Subjects who have received a complete three-dose primary vaccination with diphtheria-tetanus-acellular pertussis (DTPa) vaccine and inactivated poliovirus (IPV) vaccine in the first six months of life, in line with recommendations in the United Kingdom (UK). Subjects who received a first dose of a live attenuated measles-mumps-rubella vaccine within the second year of life, in line with recommendations in the UK. Written informed consent obtained from the parent(s)/LAR(s) of the subject at the time of enrolment. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the booster 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, with the exception of inactivated influenza vaccine. 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 diphtheria, tetanus, pertussis, poliomyelitis since primary vaccination in the first year of life. Previous measles, mumps and/or rubella second dose vaccination. Evidence of previous or intercurrent diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps and/or rubella disease. Known exposure to measles, mumps and/or rubella within 30 days prior to study start. Any confirmed or suspected immunosuppressive or immunodeficiency condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Administration of immunoglobulin and/or any blood products within the three months preceding the booster dose or planned administration during the study period. Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation. 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. Acute disease and/or fever at the time of enrolment or within 24 hours of study vaccine administration.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 4 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 of 3 or 4 years of age, who were previously vaccinated with 3 doses of Infanrix™ and Polio™ vaccines in the German household contact study (APV-039), additionally received 1 booster dose of Boostrix™ Polio vaccine co-administered with Priorix™ vaccine at Day 0. Boostrix™ Polio vaccine was administered intramuscularly in the deltoid muscle of the left arm, while Priorix™ vaccine was administered subcutaneously in the deltoid region of the right arm or as an intramuscular injection into the deltoid muscle of the right arm. | Biological: Boostrix PolioTM<br>* Single dose, intramuscular administration.<br>Biological: PriorixTM<br>* Single dose, intramuscular or subcutaneous administration.<br>|
| Active Comparator: REPEVAX GROUP<br>Healthy male or female children of 3 or 4 years of age, who were previously vaccinated with 3 doses of Infanrix™ and Polio™ vaccines in the German household contact study (APV-039), additionally received 1 booster dose of Repevax™ vaccine co-administered with Priorix™ vaccine at Day 0. Repevax™ vaccine was administered intramuscularly in the deltoid muscle of the arm, while Priorix™ vaccine was administered subcutaneously in the deltoid region of the right arn or as an intramuscular injection into the deltoid muscle of the right arm. | Biological: RepevaxTM<br>* Single dose, intramuscular administration.<br>Biological: PriorixTM<br>* Single dose, intramuscular or subcutaneous administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Booster Response to Diphtheria (D) and Tetanus (T) Antigens | Booster response was defined as: For initially seronegative subjects [i.e. pre-vaccination concentration below (<) cut-off value of 0.1 international units per milliliter (IU/mL)] antibody concentrations at least four times the assay cut-off [post vaccination concentration greater than or equal to (≥) 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 booster vaccination concentration. | At Month 1, one month after the booster vaccination | 
| Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Month 1, one month after the booster vaccination | 
| Anti-Polio Virus Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | At Month 1, one month after the booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) | A seroprotected subject was defined a subject with anti-D and anti-T antibody concentrations ≥ 0.1 international units per millilitre (IU/mL). | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN | A seropositive subject for anti-PT, anti-FHA and anti-PRN was a subject whose antibody concentration was ≥ 5 EL.U/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroprotected Subjects Against Polio Type 1, 2 and 3 | A seroprotected subject was defined as a subject with anti-polio type 1, 2 and 3 antibody titres ≥ the value of 8. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seropositive Subjects for Anti-measles Antibody | A seropositive subject was defined as a subject with anti-measles antibody titers ≥ 150 mIU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seropositive Subjects for Anti-mumps Antibody | A seropositive subject was defined as a subject with anti-mumps antibody titers ≥ 231 U/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seropositive Subjects for Anti-rubella Antibody | A seropositive subject was defined as a subject with anti-rubella antibody titers ≥ 4 IU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. | At Month 0, before the booster vaccination | 
| Anti-mumps Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in U/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-measles Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-rubella Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-Polio Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | At Month 0, before the booster vaccination | 
| Number of Subjects With a Booster Response to PT, FHA and PRN Antigens | Booster response was defined as: For initially seronegative subjects (pre-vaccination concentration < 5 EL.U/mL), antibody concentrations at least four times the assay 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 booster 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 booster vaccination concentration. | At Month 1, one month after the booster vaccination | 
| Number of Subjects With Booster Response for Polio Type 1, 2 and 3 Antigens | Booster response defined as: For initially seronegative subjects, antibody titers at least four times the cut-off (post-vaccination titer ≥ 32); For initially seropositive subjects, an increase in antibody titers of at least four times the Pre booster vaccination titer. | At Month 1, one month after the booster vaccination | 
| Number of Seroconverted Subjects for Anti-measles | Seroconversion for anti-measles was defined as the appearance of antibodies after vaccination in subjects who were initially seronegative [with antibody concentrations ≥ 150 milli-international units per millilitre (mIU/mL)]. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroconverted Subjects for Anti-mumps | Seroconversion for anti-mumps was defined as the appearance of antibodies after vaccination in subjects who were initially seronegative [with antibody concentrations ≥ 231 units per millilitre (U/mL)]. | Before (Month 0) and one month after (Month 1) the booster 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) follow-up period after booster vaccination | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite 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) follow-up period after booster vaccination | 
| 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) follow-up period after booster vaccination | 
| 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 entire study period (From Day 0 to Month 1) | 

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