Immunogenicity and Safety Study of Booster Dose of GSK Biologicals' IPV (Poliorix™) and DTPa/Hib (Infanrix+Hib™) Vaccine

Study Overview
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Brief Summary
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The purpose of this booster study is to evaluate the immune persistence in healthy Chinese subjects primed in study NCT01086423 with GSK Biologicals' Infanrix-IPV+Hib™ (DTPa-IPV/Hib) vaccine. The study will also evaluate the safety and immune response of these subjects to a booster dose of Infanrix-Hib™ (DTPa/Hib) and Poliorix™ (IPV) vaccine. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT01086423).

Official Title
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Immunogenicity and Safety of a Booster Dose of GlaxoSmithKline Biologicals' IPV (Poliorix™) and DTPa/Hib (Infanrix+Hib™) in Healthy Chinese Toddlers

Conditions
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Acellular Pertussis, Tetanus, Diphtheria, Haemophilus Influenzae Type b

Intervention / Treatment
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* Biological: Infanrix+Hib™
* Biological: Poliorix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female child between, and including, 18 and 24 months of age at the time of the booster vaccination. Subjects who completed the full three-dose primary vaccination course in study NCT01086423. Subjects who the investigator believes that their parent(s)/ Legally Acceptable Representative(s) LAR(s) can and will comply with the requirements of the protocol Written informed consent obtained from the parent(s)/LAR(s) of the subject. 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 the 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 dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to the booster vaccination, or planned administration during the study period. Participation in another clinical study within three months prior to enrolment in the present booster study or at any time during the present booster study, in which the subject has been or will be exposed to an investigational or a non-investigational product. Evidence of previous diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b, vaccination or disease since the conclusion visit of primary study NCT01086423. Serious chronic illness. Administration of immunoglobulins and/or any blood products within the 90 days preceding the booster dose of study vaccine or planned administration during the study period. Occurrence of any of the following adverse events after a previous administration of a DTP vaccine. Encephalopathy Temperature of ≥ 40.0°C (axillary temperature) within 48 hours of vaccination, not due to another identifiable cause. Collapse or shock-like state within 48 hours of vaccination. Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting ≥ 3 hours. Seizures with or without fever occurring within 3 days of vaccination. 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: Acute disease and/or fever at the time of enrolment.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 24 Months

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: INFANRIX+HIB/POLIORIX 1 GROUP<br>Healthy male or female children between, and including, 18 and 24 months of age at the time of booster vaccination, who were primed with 3 doses of the Infanrix-IPV/Hib™ vaccine at 2, 3 and 4 months of age in the DTPA-IPV-056 (112584) primary study, additionally received 1 dose of Poliorix™ and of Infanrix+Hib™ vaccines, administered intramuscularly into the upper sides of the left and right thighs, respectively. | Biological: Infanrix+Hib™<br>* Intramuscular, one dose<br>* Other names: DTPa /Hib;Biological: Poliorix™<br>* Intramuscular, one dose<br>* Other names: IPV;|
| Experimental: INFANRIX+HIB/POLIORIX 2 GROUP<br>Healthy male or female children between, and including, 18 and 24 months of age at the time of booster vaccination, who were primed with 3 doses of the Infanrix-IPV/Hib™ vaccine at 3, 4 and 5 months of age in the DTPA-IPV-056 (112584) primary study, additionally received 1 dose of Poliorix™ and of Infanrix+Hib™ vaccines, administered intramuscularly into the upper sides of the left and right thighs, respectively. | Biological: Infanrix+Hib™<br>* Intramuscular, one dose<br>* Other names: DTPa /Hib;Biological: Poliorix™<br>* Intramuscular, one dose<br>* Other names: IPV;|
| Active Comparator: CONTROL GROUP<br>Healthy male or female children between, and including, 18 and 24 months of age at the time of booster vaccination, who were primed with 3 doses of the Infanrix+Hib™ and of Poliorix™ vaccines at 2, 3 and 4 months of age in the DTPA-IPV-056 (112584) primary study, additionally received 1 dose of Poliorix™ and of Infanrix+Hib™ vaccines, administered intramuscularly into the upper sides of the left and right thighs, respectively. | Biological: Infanrix+Hib™<br>* Intramuscular, one dose<br>* Other names: DTPa /Hib;Biological: Poliorix™<br>* Intramuscular, one dose<br>* Other names: IPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a vaccinated subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). | Before the booster vaccination (At Day 0) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥0.1 IU/mL. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (Anti-PRP) | A seroprotected subject was defined as a vaccinated subject with anti-PRP antibody concentration ≥ 0.15 micrograms per milliliter (µg/mL). | Before the booster vaccination (At Day 0) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 µg/mL. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against Polio Type 1, 2 and 3 | A seroprotected subject was defined as a vaccinated subject with anti-polio type 1, 2 and 3 antibody concentrations ≥ the cut-off value of 8 Estimated Dose 50% (ED50). ED50 is the estimated serum dilution reducing the signal generated by viral infection with 50%. | Before the booster vaccination (At Day 0) | 
| Anti-polio Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs) for the seroprotection cut-off of ≥ 8. | Before the booster vaccination (At Day 0) | 
| Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) | A seropositive subject was defined as a vaccinated subject with anti-PT, anti-FHA and anti-PRN antibody concentration ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml). | Before the booster vaccination (At Day 0) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a vaccinated subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 IU/mL. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a vaccinated subject with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.1 IU/mL. | Before the booster vaccination (At Day 0) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as GMCs for the seroprotection cut-off of ≥ 0.1 IU/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) | A seroprotected subject was defined as a vaccinated subject with anti-PRP antibody concentration ≥ 0.15 µg/mL. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against PRP | A seroprotected subject was defined as a vaccinated subject with anti-PRP antibody concentrations ≥ 0.15 µg/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 micrograms per milliliter (µg/mL). | Before the booster vaccination (At Day 0) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 µg/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects for Anti-polio Type 1, 2 and 3 | A seroprotected subject was defined as a vaccinated subject with anti-polivirus antibody concentration ≥ 8 ED50. ED50 is the estimated serum dilution reducing the signal generated by viral infection with 50%. | Before the booster vaccination (At Day 0) | 
| Number of Seroprotected Subjects Against Polio Type 1, 2 and 3 | A seroprotected subject was defined as a vaccinated subject with anti-polivirus antibody concentrations ≥ 8 ED50. ED50 is the estimated serum dilution reducing the signal generated by viral infection with 50%. | One month after the booster vaccination (At Month 1) | 
| Anti-polio Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs) for the seroprotection cut-off of ≥ the value of 8. | Before the booster vaccination (At Day 0) | 
| Anti-polio Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs) for the seroprotection cut-off of ≥ 8. | One month after the booster vaccination (At Month 1) | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN | A seropositive subject was defined as a vaccinated subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 ELISA units per milliliter (EL.U/mL). | Before the booster vaccination (At Day 0) | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN | A seropositive subject was defined as a vaccinated subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 EL.U/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 5 EL.U/mL. | Before the booster vaccination (At Day 0) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrattions | Antibody concentrations were presented as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Subjects With a Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Booster response was defined as the appearance of antibodies in subjects who were initially seronegative (i.e. with concentrations < cut-off value) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e. with concentrations ≥ cut-off value), taking into consideration the decreasing maternal antibodies. | One month after the booster vaccination (At Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.1 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade and relationship to vaccination. | 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 entire study period (from Month 0 up to Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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combination vaccine, booster vaccination