Safety and Immunogenicity of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744)

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the safety and immunogenicity of new formulations of GSK Biologicals' DTPa-HBV-IPV/Hib vaccine (GSK217744) when administered as a primary vaccination course to healthy infants at 2, 3 and 4 months of age.

Detailed Description
-----------------
This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the exclusion criteria.

Official Title
-----------------
Safety and Immunogenicity of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744) in Primary Infant Vaccination

Conditions
-----------------
Tetanus, Poliomyelitis, Hepatitis B, Haemophilus Influenzae Type b, Acellular Pertussis, Diphtheria

Intervention / Treatment
-----------------
* Biological: Infanrix hexa™
* Biological: Prevenar 13®
* Biological: GSK217744


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female between, and including, 60 and 90 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 their 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 vaccines within 30 days preceding the first dose of study vaccine, 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, or planned administration during the study period, with the exception of oral rotavirus vaccination which is allowed at any time during the study. 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, polio, hepatitis B, Hib and/or pneumococcal vaccination or disease, with the exception of hepatitis B vaccination at birth. 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
-----------------
Minimum Age: 60 Days
Maximum Age: 90 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK217744 Group 1<br>Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively. | Biological: Prevenar 13®<br>* 3 co-administered doses, intramuscular into right thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: GSK217744<br>* 3 doses, intramuscular into left thigh<br>|
| Experimental: GSK217744 Group 2<br>Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively. | Biological: Prevenar 13®<br>* 3 co-administered doses, intramuscular into right thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: GSK217744<br>* 3 doses, intramuscular into left thigh<br>|
| Active Comparator: Infanrix hexa Group<br>Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa™ vaccine, co-administered with Prevenar 13® at 2, 3 and 4 months of age. The Infanrix hexa™ and Prevenar 13® vaccines were administered intramuscularly into the left and right sides of the thigh, respectively. | Biological: Infanrix hexa™<br>* 3 doses, intramuscular into left thigh<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Prevenar 13®<br>* 3 co-administered doses, intramuscular into right thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;|

What is the study measuring?
-----------------
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 anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/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 anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | At Month 3 | 
| Concentrations for Anti-pertussis Toxoid (Anti-PT) and Anti-pertactin (Anti-PRN) Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL). | At Month 0 | 
| Concentrations for Anti-pertussis Toxoid (Anti-PT) and Anti-pertactin (Anti-PRN) Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL). | At Month 3 | 
| Number of Seroprotected Subjects for Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 3 | 
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 10 and 100 Milli-International Units Per Milliliter (mIU/mL) | A seroprotected subject was defined as a vaccinated subject who had anti-HBs antibody concentrations ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | At Month 3 | 
| Concentrations for Anti-HBs Antibodies ≥ 10 and 100 mIU/mL | A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. Concentrations were expressed as geometric mean concentrations (GMCs) in milli-International units per milliliter (mIU/mL). | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL. | At Months 0 and 3 | 
| Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT) and Anti-pertactin (Anti-PRN) Antibodies. | A seropositive subject was defined as a vaccinated subject who had anti-PT and anti-PRN antibody concentrations ≥ 5 EL.U/mL. | At Months 0 and 3 | 
| Concentrations for Anti-polyribosyl-ribitol-phosphate (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 3 | 
| Number of Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes. | A seropositive subject was defined as a vaccinated subject who had anti- pneumococcal antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. | At Month 3 | 
| Concentrations for Anti-PNE Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 0.15 µg /mL. The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. | At Month 3 | 
| Number of Subjects With a Vaccine Response to PT and PRN. | Vaccine response defined as: for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL at 1 month post primary vaccination (Month 3); for initially seropositive subjects, antibody concentration at 1 month post primary vaccination (Month 3) ≥ 1 fold the pre-vaccination antibody concentration. | At Month 3 | 
| Number of Subjects Reporting Any Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. | During the 8-day (Days 0-7) | 
| Number of Subjects Reporting Any Solicited General Symptoms. | Solicited local symptoms assessed were drowsiness, irritability, loss of appetite and fever [axillary temperature above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of any local symptom regardless of intensity grade. | During the 8-day (Days 0-7) | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs). | An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 = occurrence of an AE regardless of intensity grade or relationship to study vaccination. | Within the 31-day (Days 0-30) follow up period after vaccination. | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Any SAE = any SAE regardless of assessment of relationship to study vaccination. | During the entire study period (Month 0 to Month 3) | 

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