Evaluation of the Immunogenicity, Safety and Reactogenicity of the Combined DTPa-IPV Vaccine in Healthy Infants

Study Overview
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Brief Summary
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DTPa and IPV vaccines are recommended for immunization of infants in Korea. The use of combination vaccines simplifies routine paediatric vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Participants in this Phase IIIb study will either receive GSK Biologicals' combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV) vaccine or co-administration of GSK Biologicals' combined diphtheria-tetanus-acellular pertussis (DTPa) vaccine and Sanofi-Pasteurs' inactivated poliovirus vaccine. Vaccines for both groups will be administered at 2, 4 and 6 months of age. Two blood samples will be collected during the course of the study: prior to vaccination and one month after the third vaccine dose.

Official Title
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A Multicentric Study to Compare the Immunogenicity, Safety & Reactogenicity of GSK Biologicals' DTPa-IPV Vaccine vs. Co-administration of GSK's DTPa Vaccine & Sanofi-Pasteurs' IPV Vaccine at Different Injection Sites, to Healthy Children

Conditions
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Tetanus, Acellular Pertussis, Diphtheria

Intervention / Treatment
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* Biological: DTPa-IPV
* Biological: DTPa
* Biological: IMOVAX Polio®


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol . A male or female between, and including, 8 and 12 weeks (56-90 days) of age at the time of the first vaccination. 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. Born after a gestation period of 36 to 42 weeks inclusive. Exclusion criteria: Use of any investigational or non-registered product (drug or vaccine) 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 (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. Administration of any vaccine within 30 days (i.e.30 days to 1 day) before the first dose of the study vaccine. Planned administration/ administration of a vaccine not foreseen by the study protocol during the study period (i.e. Day 0 to Month 7), with the exception of Bacille Calmette-Guérin (BCG) vaccine, hepatitis B vaccine, pneumococcal vaccine, flu vaccine and Hib vaccine. Planned administration/ administration of a vaccine foreseen by the study protocol (i.e. BCG vaccine, hepatitis B vaccine, pneumococcal, flu vaccine and Hib vaccine) during the period 30 days before and one week after the study vaccine dose. 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 (pharmaceutical product or device). Previous vaccination against diphtheria, tetanus, pertussis and/or poliovirus disease. History of diphtheria, tetanus, pertussis and/or poliovirus diseases. Known exposure to diphtheria, tetanus, pertussis and/or poliovirus before the study period. Any anaemia/ thrombocytopenia or blood clot that leads to prohibition from intramuscular injection. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at the time of enrolment Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 8 Weeks
Maximum Age: 12 Weeks

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-IPV Group<br>Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' combined Infanrix™-IPV (DTPa-IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral thigh. | Biological: DTPa-IPV<br>* 3 intramuscular injections<br>* Other names: Infanrix™-IPV;|
| Active Comparator: Infanrix + IMOVAX Polio Group<br>Healthy male or female subjects between and including 8 to 12 weeks (56-90 days) of age at the time of the first vaccination, who were born after a gestation period of 36 to 42 weeks, received 3 doses of the GSK Biologicals' Infanrix™ (DTPa) vaccine co-administered with Sanofi-Pasteur's IMOVAX Polio® (IPV) vaccine at 2, 4 and 6 months of age, intramuscularly into the antero-lateral sides of opposite thighs. | Biological: DTPa<br>* 3 intramuscular injections<br>* Other names: Infanrix™;Biological: IMOVAX Polio®<br>* 3 intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) | A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 0.1 international units/milliliter (IU//mL). | One month (Month 5) post-primary vaccination course | 
| Number of Seroprotected Subjects Against Poliovirus (Anti-polio) Types 1, 2 and 3 | A seroprotected subject was defined as a vaccinated subject with anti-poliovirus types 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers greater than or equal to (≥) the cut-off value of 8. | One month (Month 5) post-primary vaccination course | 
| Number of Subjects With a Vaccine Response for Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Haemagglutinin (Anti-FHA) | Vaccine response was defined as: - for initially seronegative subjects, antibody concentrations ≥ 5 EL.U/mL one month after third vaccine dose; - for initially seropositive subjects, at least maintenance of pre-vaccination antibody concentrations one month after third vaccine dose. | One month (Month 5) post-primary vaccination course | 
| Number of Subjects With Vaccine Response to Pertussis Toxoid (PT), Pertactin (PRN) and Filamentous Haemagglutinin (FHA) Antigens | Vaccine response to pertussis toxoid (PT), pertactin (PRN) and filamentous haemagglutinin (FHA) was defined as the appearance of antibodies in subjects who were initially (i.e. before vaccination) seronegative (i.e. with concentrations < 5 EL.U/mL), or at least as the maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e. with concentrations ≥ 5 EL.U/mL value). | One month (Month 5) post-primary vaccination course | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) | A seroprotected subject was defined as a vaccinated subject with anti-diphteria (anti-D) and anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) the cut-off value of 1 international units/milliliter (IU//mL). | Before (Pre) and one month after (Post) the primary vaccination course | 
| Concentration of Antibodies Against Diphteria (Anti-D) and Tetanus (Anti-T) | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per millilitre (mIU/mL). | Before (Pre) and one month after (Post) the primary vaccination course | 
| Titers for Poliovirus Type 1, 2 and 3 Antibodies | Titers for anti-polio 1, 2 and 3 are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was greater than or equal to (≥) 8. | Before (Pre) and one month after (Post) the primary vaccination course | 
| Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Pertactin (Anti-PRN) and Filamentous Haemagglutinin (Anti-FHA) | Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL). | Before (Pre) and one month after (Post) the primary vaccination course | 
| Number of Subjects Reporting Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = crying when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site. | During the 4-day (Days 0-3) post-vaccination period, across doses | 
| Number of Subjects Reporting Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = symptom symptoms considered by the investigator to have a causal relationship to vaccination. | During the 4-day (Days 0-3) post-vaccination period, across doses | 
| Number of Subjects Reporting 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 Reporting Any 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 5) |