Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine in Healthy Infants

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of GSK Biologicals' GSK2202083 vaccine co-administered with Prevenar 13® at 2, 4 and 12 months of age and with Rotarix™ at 2 and 4 months of age.

Official Title
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Feasibility Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine in Healthy Infants at 2, 4 and 12 Months of Age

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

Intervention / Treatment
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* Biological: GSK2202083A vaccine
* Biological: Prevenar 13®
* Biological: Infanrix hexa™
* Biological: Menjugate®
* Biological: Rotarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) can and will comply with the requirements of the protocol. A male or female infant between, and including, 8 and 12 weeks at the time of the first vaccination. Born after a gestation period of 36 to 42 weeks inclusive. 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: Use of any investigational or non-registered product 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 of immunosuppressants or other immune-modifying drugs since birth. Child in care. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Administration of a vaccine not foreseen by the study protocol within 30 days prior to randomisation, or planned administration from randomisation to the end of the study with the exception of inactivated influenza vaccines. The administration of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, pneumococcal, rotavirus and/or MenC vaccines is not allowed at any time during the study period but other vaccines are allowed during the period from one day after study Visit 3 to 31 days before study Visit 4. 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 diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Hib, pneumococcal, rotavirus and/or MenC vaccination or disease, including Hepatitis B virus vaccination at birth. History of seizures or progressive neurological disease. Subjects with history of intussusception or uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception. 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 vaccine(s). 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 other moderate to severe illness within 24 hours of study vaccine administration. Current gastrointestinal infection.

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 Group<br>Subjects aged between and including 8 and 12 weeks of age at the time of first vaccination received 3 doses of GSK2202083A vaccine, co-administered with Prevenar 13® at 2, 4 and 12 months of age. The GSK2202083A and Prevenar 13® vaccines were administered intramuscularly into the right and left sides of the thigh, respectively. An optional 2-dose vaccination with Rotarix™ was offered to the study participants at 2 and 4 months of age. | Biological: GSK2202083A vaccine<br>* 3 doses given at 2, 4 and 12 months of age<br>Biological: Prevenar 13®<br>* 3 co-administered doses<br>Biological: Rotarix™<br>* Oral, two doses<br>|
| Active Comparator: Infanrix hexa Group<br>Subjects aged between and including 8 and 12 weeks of age at the time of first vaccination received 3 doses of Infanrix hexa™ vaccine, co-administered with Prevenar 13® and Menjugate® at 2, 4 and 12 months of age. The Infanrix hexa™ and Prevenar 13® vaccines were administered intramuscularly into the right and upper left sides of the thigh, respectively and the Menjugate® vaccine was administered intramuscularly in the lower left thigh. An optional 2-dose vaccination with Rotarix™ was offered to the study participants at 2 and 4 months of age. | Biological: Prevenar 13®<br>* 3 co-administered doses<br>Biological: Infanrix hexa™<br>* 3 doses given at 2, 4 and 12 months of age<br>Biological: Menjugate®<br>* 3 co-administered doses<br>Biological: Rotarix™<br>* Oral, two doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Above the Cut-off | The anti-PRP antibody concentration cut-off for this assay was greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL). | At Month 3 | 
| Number of Subjects With Neisseria Meningitidis Using Baby Rabbit Complement (rSBA-MenC) Antibody Titers Above the Cut-off | The rSBA-MenC antibody titers cut-off for this assay was ≥ 1:8. | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-PRP Antibody Concentrations Above the Cut-offs | The anti-PRP antibody concentration cut-offs for this assay were ≥ 0.15 µg/mL and 1.0 µg/mL. Values concerning the cut-off of 0.15 µg/mL at Month 3 were listed for a primary outcome, hence they were not reported under this outcome. | At Month 3, Month 10 and Month 11. | 
| Number of Subjects With rSBA-MenC Antibody Titers Above the Cut-offs | The rSBA-MenC antibody titers cut-off for this assay were ≥ 1:8 and ≥ 1:128. Values concerning the cut-off of 1:8 at Month 3 were listed for a primary outcome, hence they were not reported under this outcome. | At Month 3, Month 10 and Month 11. | 
| Concentrations for Anti-PRP. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off values were ≥ 0.15 µg/mL and ≥ 1.0 µg/mL. | At Month 3, Month 10 and Month 11. | 
| Titers for rSBA-MenC. | Titers were expressed as geometric mean titers (GMCs). The seropositivity reference cut-off values were ≥ 1:8 and ≥ 1:128. | At Month 3, Month 10 and Month 11. | 
| Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies Above the Cut-off. | The anti-D and anti-T antibody cut-off was ≥ 0.1 international units per milliliter (IU/mL). | At Month 3, Month 10 and Month 11. | 
| Concentrations for Anti-T and Anti-D. | Concentrations were expressed as geometric mean concentrations (GMCs). The reference cut-off value was ≥ 0.1 IU/mL. | At Month 3, Month 10 and Month 11. | 
| 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 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, Month 10 and Month 11. | 
| Concentrations for Anti-HBs. | 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, Month 10 and Month 11. | 
| Number of Subjects With Anti-poliovirus (Anti-polio) Types 1, 2 and 3 Above the Cut-off. | The anti-polio 1, 2 and 3 antibody concentrations cut-off value was ≥ 1:8. | At Month 3, Month 10 and Month 11. | 
| Titers for Anti-polio 1, 2 and 3. | Titers were expressed as geometric mean titers (GMTs). The reference cut-off value was ≥ 1:8. | At Month 3, Month 10 and Month 11. | 
| Number Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Above the Cut-off. | The reference cut-off for anti-PT, anti-FHA and anti-PRN antibody concentrations was ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL). | At Month 3, Month 10 and Month 11. | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN. | Concentrations were expressed as geometric mean concentrations (GMCs). The reference cut-off value was ≥ 5 EL.U/mL. | At Month 3, Month 10 and Month 11. | 
| Number of Subjects With a Booster Response to Anti-PT, Anti-FHA and Anti-PRN. | Booster response defined as: for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL at Month 11; for initially seropositive subjects: antibody concentration at Month 11 ≥ 2 fold the pre-vaccination antibody concentration | At Month 11. | 
| Number of Subjects With Anti-pneumococcal (Anti-PNE) Serotypes Above the Cut-offs. | The anti-PNE antibody concentrations reference cut-offs were ≥ 0.2 and ≥ 0.05 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 and Month 11 | 
| Concentrations for Anti-PNE Serotypes. | Concentrations were expressed as geometric mean concentreations (GMCs). The reference cut-off value was ≥ 0.2 µg/mL. | At Month 3 and Month 11 | 
| Number of Subjects With Anti-PRP and rSBA-MenC Fold Increase Distribution. | The fold increase distribution cut-offs were: ≥2, ≥4, ≥6, ≥8 and ≥10. | At Month 11. | 
| 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) post-vaccination period | 
| Number of Subjects Reporting Any Solicited General Symptoms. | Solicited local symptoms assessed were drowsiness, irritability/fussiness, 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) post-vaccination period | 
| 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 11) |