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

Phase 3

Completed

Conditions: Diphtheria
Acellular Pertussis
Poliomyelitis
Tetanus

Interventions: Biological: Boostrix PolioTM
Biological: RepevaxTM
Biological: PriorixTM

Registration Number: NCT01245049

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 387

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BOOSTRIX POLIO GROUP	Boostrix PolioTM	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.
BOOSTRIX POLIO GROUP	PriorixTM	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.
REPEVAX GROUP	RepevaxTM	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.
REPEVAX GROUP	PriorixTM	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With a Booster Response to Diphtheria (D) and Tetanus (T) Antigens	At Month 1, one month after the booster vaccination	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.
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations	At Month 1, one month after the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Anti-Polio Virus Type 1, 2 and 3 Antibody Titers	At Month 1, one month after the booster vaccination	Antibody titers were presented as geometric mean titers (GMTs).

Secondary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T)	Before (Month 0) and one month after (Month 1) the booster vaccination	A seroprotected subject was defined a subject with anti-D and anti-T antibody concentrations ≥ 0.1 international units per millilitre (IU/mL).
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN	Before (Month 0) and one month after (Month 1) the booster vaccination	A seropositive subject for anti-PT, anti-FHA and anti-PRN was a subject whose antibody concentration was ≥ 5 EL.U/mL.
Number of Seroprotected Subjects Against Polio Type 1, 2 and 3	Before (Month 0) and one month after (Month 1) the booster vaccination	A seroprotected subject was defined as a subject with anti-polio type 1, 2 and 3 antibody titres ≥ the value of 8.
Number of Seropositive Subjects for Anti-mumps Antibody	Before (Month 0) and one month after (Month 1) the booster vaccination	A seropositive subject was defined as a subject with anti-mumps antibody titers ≥ 231 U/mL.
Number of Seropositive Subjects for Anti-rubella Antibody	Before (Month 0) and one month after (Month 1) the booster vaccination	A seropositive subject was defined as a subject with anti-rubella antibody titers ≥ 4 IU/mL.
Number of Seropositive Subjects for Anti-measles Antibody	Before (Month 0) and one month after (Month 1) the booster vaccination	A seropositive subject was defined as a subject with anti-measles antibody titers ≥ 150 mIU/mL.
Anti-D and Anti-T Antibody Concentrations	Before (Month 0) and one month after (Month 1) the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL.
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	At Month 0, before the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL.
Anti-mumps Antibody Concentrations	Before (Month 0) and one month after (Month 1) the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in U/mL.
Anti-measles Antibody Concentrations	Before (Month 0) and one month after (Month 1) the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL.
Anti-rubella Antibody Concentrations	Before (Month 0) and one month after (Month 1) the booster vaccination	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL.
Anti-Polio Type 1, 2 and 3 Antibody Titers	At Month 0, before the booster vaccination	Antibody titers were presented as geometric mean titers (GMTs).
Number of Subjects With a Booster Response to PT, FHA and PRN Antigens	At Month 1, one month after the booster vaccination	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.
Number of Subjects With Booster Response for Polio Type 1, 2 and 3 Antigens	At Month 1, one month after the booster vaccination	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.
Number of Seroconverted Subjects for Anti-measles	Before (Month 0) and one month after (Month 1) the booster vaccination	Seroconversion for anti-measles was defined as the appearance of antibodies after vaccination in subjects who were initially seronegative \[with antibody concentrations ≥ 150 milli-international units per millilitre (mIU/mL)\].
Number of Seroconverted Subjects for Anti-mumps	Before (Month 0) and one month after (Month 1) the booster vaccination	Seroconversion for anti-mumps was defined as the appearance of antibodies after vaccination in subjects who were initially seronegative \[with antibody concentrations ≥ 231 units per millilitre (U/mL)\].
Number of Subjects With Any Solicited Local Symptoms	During the 4-day (Days 0-3) follow-up period after booster vaccination	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Any Solicited General Symptoms	During the 4-day (Days 0-3) follow-up period after booster vaccination	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.
Number of Subjects With Any Unsolicited Adverse Events (AEs)	During the 31-day (Days 0-30) follow-up period after booster vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs)	During the entire study period (From Day 0 to Month 1)	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.