Immunogenicity and Safety of GlaxoSmithKline Biologicals' Infanrix™-IPV+Hib Vaccine

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and immunogenicity of Infanrix™-IPV+Hib vaccine when administered as a primary vaccination course to healthy Korean infants at 2, 4 and 6 months of age.

Official Title
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Immunogenicity and Safety of GlaxoSmithKline Biologicals' DTPa-IPV/Hib (Infanrix™-IPV+Hib) Vaccine in Healthy Korean Infants

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

Intervention / Treatment
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* Biological: Infanrix™-IPV+Hib
* Biological: Infanrix™ IPV
* Biological: Hiberix™
* Biological: Synflorix™
* Biological: Rotarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female between, and including, 42 and 69 days of age at the time of the first vaccination. Born after a gestation period of 37 to 42 weeks inclusive. Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) can and will comply with the requirements of the protocol. Written informed consent obtained from the parent(s)/ Legally Acceptable Representative(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 first dose, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Administration of a vaccine not foreseen by the study protocol, within 30 days prior to the first study visit, with the exception of hepatitis B and Bacillus Calmette-Guérin vaccination; or planned administration during the study period, with the exception of hepatitis B and influenza vaccines, which will be allowed at least 7 days before or 30 days after the administration of the DTPa 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. Evidence of previous or intercurrent diphtheria, tetanus, pertussis, poliomyelitis and Hib vaccination or disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Family history of congenital or hereditary immunodeficiency. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. History of any neurological disorders or seizures. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Acute disease and/or fever at the time of enrolment.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 69 Days

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+Hib Group<br>Subjects aged between, and including, 42 and 69 days at the time of first vaccination received 3 doses of Infanrix™-IPV+Hib at 2, 4 and 6 months of age, 3 doses of Synflorix™ at 6 weeks, 3.5 and 5.5 months of age and 2 doses of Rotarix™ at 6 weeks and 3.5 months of age. The Infanrix™-IPV+Hib was administered intramuscularly in the right thigh, the Synflorix™ vaccine was administered intramuscularly in the left thigh and the Rotarix™ vaccine was administered orally. | Biological: Infanrix™-IPV+Hib<br>* Intramuscular, 3 doses<br>Biological: Synflorix™<br>* Intramuscular, 3 doses<br>Biological: Rotarix™<br>* Oral, 2 doses<br>|
| Active Comparator: Infanrix IPV Group<br>Subjects aged between, and including, 42 and 69 days at the time of first vaccination received 3 doses of Infanrix™ IPV and Hiberix™ co-administered at separate injection sites at 2, 4 and 6 months of age, 3 dose of Synflorix™ at 6 weeks, 3.5 and 5.5 months of age and 2 doses of Rotarix™ at 6 weeks and 3.5 months of age. The Infanrix™ IPV was administered intramuscularly in the right thigh, the Synflorix™ and Hiberix™ vaccines were administered intramuscularly in the left thigh and the Rotarix™ vaccine was administered orally. | Biological: Infanrix™ IPV<br>* Intramuscular, 3 doses<br>Biological: Hiberix™<br>* Intramuscular, 3 doses<br>Biological: Synflorix™<br>* Intramuscular, 3 doses<br>Biological: Rotarix™<br>* Oral, 2 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had an anti-D and anti-T antibody concentration equal to or above (≥) 0.1 international units per milliliter (IU/mL). | At Month 5 | 
| Number of Seroprotected Subjects for Anti-poliovirus (Anti-polio) Types 1, 2 and 3. | A seroprotected subject was defined as a vaccinated subject who had an anti-polio types 1, 2 and 3 antibody titres equal to or above (≥) 8, cut off corresponding to the effective dose for 50% of the vaccinated subjects. | At Month 5 | 
| Number of Seroprotected Subjects for Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had an anti-PRP antibody concentration ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 5 | 
| Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations. | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of 5 ELISA units per milliliter (EL.U/mL). | At Month 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN). | A seropositive subjects was defined as a vaccinated subjects who had an anti-PRN, anti-PT and anti-FHA antibody concentration ≥ 5 ELISA units per milliliter (EL.U/mL). | At Month 0 and Month 5 | 
| Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of 5 EL.U/mL. | At Month 0 | 
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had an anti-D and anti-T antibody concentration equal to or above (≥) 0.1 international units per milliliter (IU/mL). | At Month 0 | 
| Concentrations for Anti-D and Anti-T Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL. | At Month 0 and Month 5 | 
| Number of Seroprotected Subjects Anti-poliovirus (Anti-polio) Types 1, 2 and 3. | A seroprotected subject was defined as a vaccinated subject who had an anti-polio types 1, 2 and 3 antibody titres equal to or above (≥) 8, cut off corresponding to the effective dose for 50% of the vaccinated subjects. | At Month 0 | 
| Titres for Anti-polio Types 1, 2 and 3. | Titres were expressed as geometric mean titres (GMTs). The seroprotection cut-off of the assay was 8. | At Month 0 and Month 5 | 
| Number of Seroprotected Subjects for Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had an anti-PRP antibody concentration ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 0 | 
| Concentrations of Anti-PRP Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.15 µg/mL. | At Month 0 and Month 5 | 
| Number of Subjects With a Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN. | Vaccine response was defined as antibody concentration ≥ 5 EL.U/mL at post vaccination, for initially seronegative subjects, and at least maintenance of antibody concentration from pre to post-vaccination (i.e. antibody concentration at post vaccination ≥ 1 fold the pre-vaccination antibody concentration), for initially seropositive subjects. | At Month 5 | 
| Number of Subjects With Any Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = incidence of a particular symptom regardless of intensity grade. | During the 4-day (Days 0-3) follow-up period after any vaccination with Infanrix™-IPV+Hib or Infanrix™ IPV + Hiberix™ | 
| Number of Subjects With Any Solicited General Symptoms. | Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite and fever [defined as tympanic temperature ≥ 37.5 degrees Celsius (°C)]. Any = incidence of a particular symptom regardless of intensity grade. | During the 4-day (Days 0-3) follow-up period after any vaccination with Infanrix™-IPV+Hib or Infanrix™ IPV + Hiberix™ | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | Unsolicited AE covers any AE 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 = any unsolicited AE regardless of intensity or relationship to vaccination. | During the 31-day (Days 0-30) follow-up period after any vaccination with Infanrix™-IPV+Hib or Infanrix™ IPV + Hiberix™ | 
| Number of Subjects With 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 to Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary vaccination, combination vaccine, South Korea