Immunogenicity and Safety Study of GSK Biologicals' GSK2202083A Vaccine in Healthy Infants at 2, 3 and 4 Months of Age

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of GSK Biologicals' GSK2202083A vaccine co-administered with GSK Biologicals' 10-valent pneumococcal conjugate (GSK1024850A) vaccine given as a three-dose primary vaccination course at 2, 3 and 4 months of age.

Detailed Description
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In accordance with the local recommended immunisation schedule, all subjects will receive 2 doses of GSK Biologicals' Human Rotavirus Vaccine (Rotarix) at 2 and 3 months of age.

Official Title
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Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine in Healthy Infants at 2, 3 and 4 Months of Age

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

Intervention / Treatment
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* Biological: GSK2202083A vaccine
* Biological: 10-valent pneumococcal vaccine (GSK 1024850A)
* Biological: Infanrix hexa™
* Biological: Menjugate®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female infant between, and including, 8 and 12 weeks of age at the time of the first vaccination. Born after a gestation period of 36 to 42 weeks inclusive. Subjects should have received one dose of hepatitis B vaccination at birth as per local recommendations. Subjects who the investigator believes that their parent(s)/LAR can and will comply with the requirements of the protocol. Written informed consent obtained from the parent/LAR of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: 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 immunoglobulins and/or any blood products since birth or planned administration during the study period. Administration of any vaccine since birth, with exception of HBV and Bacillus Calmette-Guérin, or planned administration during the study period. 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, hepatitis B, polio, Hib, pneumococcal and/or MenC disease. History of seizures or progressive neurological disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Major congenital defects or serious chronic illness. 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: • Current febrile illness or axillary temperature >= 38.5 ºC or other moderate to severe illness within 24 hours of study vaccine administration.

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: GSK2202083A + SYNFLORIX GROUP<br>Healthy male and female infants between and including 8 to 12 weeks at the time of the first vaccination, who received 3 doses of GSK2202083A vaccine and Synflorix™ vaccine at 2, 3 and 4 months of age and 2 doses of Rotarix™ vaccine at 2 and 3 months of age. GSK2202083A and Synflorix™ vaccines were administered intramuscularly into the right and left thigh, while Rotarix™ vaccine was administered orally. | Biological: GSK2202083A vaccine<br>* Intramuscular, three doses<br>Biological: 10-valent pneumococcal vaccine (GSK 1024850A)<br>* Intramuscular, three doses<br>|
| Active Comparator: INFANRIX HEXA + MENJUGATE GROUP<br>Healthy male and female infants between and including 8 to 12 weeks at the time of the first vaccination, who received 3 doses of Infanrix hexa™ vaccine at 2, 3 and 4 months of age, 2 doses of Menjugate® vaccine at 3 and 4 months of age and 2 doses of Rotarix™ vaccine at 2 and 3 months of age. Infanrix hexa™ and Menjugate® vaccines were administered intramuscularly into the right and left thigh, while Rotarix™ vaccine was administered orally. | Biological: Infanrix hexa™<br>* Intramuscular, three doses<br>Biological: Menjugate®<br>* Intramuscular, two doses<br>|
| Active Comparator: INFANRIX HEXA + SYNFLORIX GROUP<br>Healthy male and female infants between and including 8 to 12 weeks at the time of the first vaccination, who received 3 doses of Infanrix hexa™ vaccine and Synflorix™ vaccine at 2, 3 and 4 months of age and 2 doses of Rotarix™ vaccine at 2 and 3 months of age. Infanrix hexa™ and Synflorix™ vaccines were administered intramuscularly into the right and left thigh, while Rotarix™ vaccine was administered orally. | Biological: 10-valent pneumococcal vaccine (GSK 1024850A)<br>* Intramuscular, three doses<br>Biological: Infanrix hexa™<br>* Intramuscular, three doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Polyribosyl-Ribitol-Phosphate (PRP) | A seroprotected subject was defined as a subject with anti-PRP antibody concentrations greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL). | At Month 3 | 
| Number of Seroprotected Subjects Against Neisseria Meningitidis Serogroup C Using Baby Rabbit Complement (rSBA-MenC) | A seroprotected subject was defined as a subject with rSBA-MenC titers greater than or equal to (≥) 1:8. | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-PRP Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off value of ≥ 0.15 µg/mL. | At Months 0 and 3 | 
| Antibody Titers Against rSBA-MenC | The seroprotection cut-off value of the assay was an antibody titer ≥ 1:8. | At Months 0 and 3 | 
| Number of Seropositive Subjects for Anti-polysaccharide Neisseria Meningitidis Serogroup C (Anti-PSC) | A seropositive subject was defined as a subject with anti-PSC antibody concentration ≥ 0.3 µg/mL. | At Month 3 | 
| Anti-PSC Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.3 µg/mL. | At Months 0 and 3 | 
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) | A seroprotected subject was defined as a subject with anti-D or anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | At Month 3 | 
| Anti-D and Anti-T Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off value of ≥ 0.1 IU/mL. | At Month 3 | 
| 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 subject with anti-PT, anti-FHA or anti-PRN concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Month 3 | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 5 EL.U/mL. | At Months 0 and 3 | 
| Number of Subjects With a Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN | A subject with a vaccine response was defined as either an initially seronegative subject with anti-PT, anti-FHA or anti-PRN concentrations ≥ 5 EL.U/mL or an initially seropositive subjects with antibody concentrations one month after the primary vaccination ≥ 1 fold the-pre vaccination antibody concentration. | At Month 3 | 
| Number of Seroprotected and Seropositive Subjects for Anti-hepatitis B Surface Antigen (Anti-HBs) | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL. A seropositive subject was defined as a subjects with anti-HBs antibody concentrations ≥ 3.3 mIU/mL. A decrease in the specificity of the anti-HB 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 | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were expressed as GMCs. The seroprotection cut-off used was of ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB 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 CLIA approved by the FDA. The table shows updated results following partial or complete retesting/reanalysis. | At Month 3 | 
| Number of Seroprotected Subjects for Anti-poliovirus (Anti-polio) Types 1, 2 and 3 | A seroprotected subject was defined as a subject with anti-polio type 1, 2 or 3 antibody titers ≥ 1:8. | At Month 3 | 
| Anti-polio Types 1, 2 and 3 Antibody Titers | Titers were expressed as geometric mean titers (GMTs) for the seroprotection cut-off value of ≥ 1:8. | At Month 3 | 
| Number of Seropositive Subjects for Anti-pneumococcal (Anti-pneumo) Serotypes | A seropositive subject was defined as a subject with anti-pneumo concentrations ≥ 0.05 µg/mL. The anti-pneumo serotypes assessed were: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | At Month 3 | 
| Anti-pneumo Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.05 µg/mL. | At Month 3 | 
| Number of Seropositive Subjects for Anti-protein D (Anti-PD) | A seropositive subject was defined as a subject with anti-PD concentrations ≥ 100 EL.U/mL. | At Month 3 | 
| Anti-PD Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 100 EL.U/mL. | At Month 3 | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = incidence of a local symptom irrespective of intensity grade. | During the 8-day (Days 0-7) post-vaccination period after any vaccination | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever (defined as axillary temperature ≥ 37.5°C). Any= incidence of a general symptom irrespective of intensity grade and relationship to vaccination. | During the 8-day (Days 0-7) post-vaccination period after any vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited AE was 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. | During the 31-day (Days 0-30) post-vaccination period after any vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. | During the entire study period (from Month 0 to Month 3) |