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

Study Overview
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Brief Summary
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The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the booster vaccine dose of 2 new formulations of DTPa-HBV-IPV/Hib administered between 12 and 15 months of age, and the immune persistence following the primary series. All children in this booster study received a primary vaccination at 2, 3 and 4 months of age in study 113948 (NCT01248884). No new subjects will be enrolled in this booster study.

Official Title
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Safety and Immunogenicity of a Booster Dose of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744)

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

Intervention / Treatment
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* Biological: Infanrix hexa
* Biological: Prevenar 13
* Biological: GSK217744


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who participated in the study 113948 (NCT01248884) and received three doses of the new or licensed DTPa-HBV-IPV/Hib study vaccine. A male or female child between, and including, 12 and 15 months of age at the time of the booster vaccination. Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit). Written informed consent obtained from the parent(s)/LAR(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 (drug or vaccine) other than the study vaccines within 30 days preceding the booster dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period. Participation in another clinical study within three months prior to enrolment in the present booster study or at any time during the present booster study, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Evidence of previous or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hib vaccination or disease since the conclusion visit of study 113948 (NCT01248884). Serious chronic illness. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. History of any neurological disorders or seizures. Administration of immunoglobulins and/or any blood products within the 3 months preceding the booster dose of study vaccine or planned administration during the study period. Occurrence of any of the following events following previous administration of the study vaccine constitutes an absolute contraindication to further dosing. Anaphylactic or other hypersensitivity reaction. Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, with failure to recover within 24 hours. Temperature of ≥ 40.0°C (axillary) or 40.5°C (rectal) within 48 hours of vaccination, not due to another identifiable cause. Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination. Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting ≥ 3 hours. Seizures with or without fever occurring within 3 days of vaccination. 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: • Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0° on rectal setting. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 15 Months

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK217744 Group 1<br>Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the GSK217744 formulation A vaccine in the primary study and a booster dose of either GSK217744 formulation A vaccine (for subjects vaccinated before Protocol Amendment 2) or Infanrix hexa vaccine (for subjects vaccinated after Protocol Amendment 2) in this study, coadministered with a booster dose of Prevenar 13. The Infanrix hexa/GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the right and left sides of the thigh, respectively. | Biological: Infanrix hexa<br>* Single dose, licensed formulation, intramuscular into right thigh<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Prevenar 13<br>* Single co-administered dose, intramuscular into left thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: GSK217744<br>* Single dose, investigational formulation A or B, intramuscular into right thigh<br>|
| Experimental: GSK217744 Group 2<br>Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the GSK217744 formulation B vaccine in the primary study and a booster dose of either GSK217744 formulation B vaccine (for subjects vaccinated before Protocol Amendment 2) or Infanrix hexa vaccine (for subjects vaccinated after Protocol Amendment 2) in this study, coadministered with a booster dose of Prevenar 13. The Infanrix hexa/GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the right and left sides of the thigh, respectively. | Biological: Infanrix hexa<br>* Single dose, licensed formulation, intramuscular into right thigh<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Prevenar 13<br>* Single co-administered dose, intramuscular into left thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: GSK217744<br>* Single dose, investigational formulation A or B, intramuscular into right thigh<br>|
| Active Comparator: Infanrix hexa Group<br>Subjects aged between and including 12 and 15 months at the time of booster vaccination who received the Infanrix hexa vaccine in the primary study and a booster dose of Infanrix hexa in this study, co-administered with a booster dose of Prevenar 13. The Infanrix hexa and Prevenar 13 vaccines were administered intramuscularly into the right and left sides of the thigh, respectively. | Biological: Infanrix hexa<br>* Single dose, licensed formulation, intramuscular into right thigh<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Prevenar 13<br>* Single co-administered dose, intramuscular into left thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;|

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 anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-D and 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). | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects Against Anti-Hepatitis B (Anti-HBs) Antigens | A seroprotected subject was a subject whose antibody concentration was greater than or equal to the level defining clinical protection of 10 milli-international units per millilitre (mIU/mL). | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects Against Anti-HBs Antigens | A seroprotected subject was a subject whose antibody concentration was greater than or equal to the level defining clinical protection of 10 milli-international units per millilitre (mIU/mL). | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3 | A seroprotected subject was a subject whose antibody titre was greater than or equal to the level defining clinical protection of 8. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-poliovirus Type 1, 2 and 3 | A seroprotected subject was a subject whose antibody titre was greater than or equal to the level defining clinical protection of 8. | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP) | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-PRP | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Concentrations for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN) | Concentrations were expressed as geometric mean concentrations (GMCs). Seropositivity cut-off assay was 5 EL.U/mL. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN | Concentrations were expressed as geometric mean concentrations (GMCs). Seropositivity cut-off assay was 5 EL.U/mL. | 1 month post booster vaccination (subjects enrolled after protocol amendment 2) | 

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. | Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| 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. | Before (PRE) 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| 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). | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-D and 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). | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Concentrations for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN) | Concentrations were expressed as geometric mean concentrations (GMCs). Seropositivity cut-off assay was 5 EL.U/mL. | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN | Concentrations were expressed as geometric mean concentrations (GMCs). Seropositivity cut-off assay was 5 EL.U/mL. | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Number of Seropositive Subjects for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN) | A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the assay cut-off of 5 ELISA units per milliliter (EL.U/mL). | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA, Anti-PRN | A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the assay cut-off of 5 ELISA units per milliliter (EL.U/mL). | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Anti-Hepatitis B (Anti-HBs) Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs). Seroprotection cut-off assay was 10 mIU/mL. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)) | 
| Anti-HBs Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs). Seroprotection cut-off assay was 10 mIU/mL. | 1 month post booster vaccination (POST) ( subjects enrolled after protocol amendment 2) | 
| Anti-Hepatitis B (Anti-HBs) Antibody Concentration | Concentrations were expressed as geometric mean concentrations (GMCs). Seroprotection cut-off assay was 10 mIU/mL. | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Anti-HBs Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs). Seroprotection cut-off assay was 10 mIU/mL. | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects Against Anti-Hepatitis B (Anti-HBs) Antigens | A seroprotected subject was a subject whose antibody concentration was greater than or equal to the level defining clinical protection of 10 milli-international units per millilitre (mIU/mL). | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects Against Anti-HBs Antigens | A seroprotected subject was a subject whose antibody concentration was greater than or equal to the level defining clinical protection of 10 milli-international units per millilitre (mIU/mL). | Before (PRE) booaster vaccination (subjects enrolled after protocol amendment 2) | 
| Concentrations for Anti-poliovirus Types 1, 2, 3 | Concentrations were expressed as geometric mean titers (GMTs). The seroprotection cut-off of the assay was 8. | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Concentration for Anti-poliovirus Types 1, 2, 3 | Concentrations were expressed as geometric mean titers (GMTs). The seroprotection cut-off of the assay was 8. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Concentrations for Anti-poliovirus Types 1, 2 and 3 | Concentrations were expressed as geometric mean titers (GMTs). The seroprotection cut-off of the assay was 8. | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Concentration for Anti-poliovirus Type 1, 2 and 3 | Concentrations were expressed as geometric mean titers (GMTs). The seroprotection cut-off of the assay was 8. | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-poliovirus Type 1, 2 and 3 | A seroprotected subject was a subject whose antibody titre was greater than or equal to the level defining clinical protection of 8. | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects Against Anti-Poliovirus Type 1, 2 and 3 | A seroprotected subject was a subject whose antibody titre was greater than or equal to the level defining clinical protection of 8. | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| 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. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Concentrations for Anti-PRP Antibodies | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.15 µg /mL. | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| 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. | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Concentrations for Anti-polyribosyl-ribitol Phosphate Antibodies | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.15 µg /mL. | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)) | 
| Number of Seropositive Subjects for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN) | A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the assay cut-off of 5 ELISA units per milliliter (EL.U/mL). | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA, Anti-PRN | A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the assay cut-off of 5 ELISA units per milliliter (EL.U/mL). | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP) | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2) | 
| Number of Seroprotected Subjects for Anti-PRP | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2) | 
| Concentrations for Anti-pneumococcal (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. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| 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. | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| 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. | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Seropositive Subjects for 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. | 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| Number of Subjects With Booster Response to Anti-pertussis Antigens (Anti-PT, Anti-FHA and Anti-PRN) | Booster response defined as : - For initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL one month after booster vaccination - For initially seropositive subjects, antibody concentration at Post-booster ≥ 2 fold the pre-vaccination antibody concentration | 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2) | 
| Number of Subjects With Booster Response to Anti-pertussis Antigens | Booster response defined as : - For initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL one month after booster vaccination - For initially seropositive subjects, antibody concentration at Post-booster ≥ 2 fold the pre-vaccination antibody concentration | 1 month poste booster vaccination (POST) (subjects enrolled after protocol amendment 2) | 
| 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 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2) | 
| Number of Subjects Reporting Any Solicited Local Symptom | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. | During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2) | 
| 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 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2) | 
| Number of Subjects Reporting Any Solicited General Symptom | 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 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2) | 
| 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. (subjects enrolled before protocol amendment 2) | 
| Number of Subjects Reporting Any Unsolicited 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. (subjects enrolled after protocol amendment 2) | 
| 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 (Days 0-30). (subjects enrolled before protocol amendment 2) | 
| Number of Subjects Reporting Any 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 (Days 0-30). (subjects enrolled after protocol amendment 2) |