Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine Administered as a Booster Dose

Phase 2

Completed

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

Interventions: Biological: GSK2202083A vaccine
Biological: Infanrix hexa™
Biological: Synflorix™
Biological: NeisVac-C™
Biological: Menjugate™

Registration Number: NCT01171989

Lead Sponsor: GlaxoSmithKline

Brief Summary: The current trial will evaluate the safety and immunogenicity of GSK Biologicals' GSK2202083A vaccine when administered as a booster dose following priming in the first year of life with the same vaccine.

This protocol posting deals with objectives \& outcome measures of the booster phase. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00970307).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 391

Inclusion Criteria

Subjects who the investigator believes that parent(s)/ legally acceptable representative(s) can and will comply with the requirements of the protocol.
Subjects who have completed the full three-dose primary vaccination course according to their group allocation in the primary study DTPa-HBV-IPV=Hib-MenC-TT-002 (112157).
A male or female between, and including, 12 and 18 months of age at the time of booster vaccination.
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 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 vaccination.
Planned administration/administration of immunoglobulins and/or any blood products within three months before the booster dose, or during the study period.
Planned administration/administration of any vaccine not foreseen by the study protocol during the period starting 30 days before and ending 30 days after the booster dose.
Participation in another clinical study since the primary study DTPa-HBV-IPV/Hib-MenC-TT-002 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 and MenC vaccination or disease since the conclusion visit of study DTPa-HBV-IPV/Hib-MenC-TT-002.
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.
The following adverse event having occurred after previous administration of DTP vaccine:
- Encephalopathy.
- Temperature of >= 40.5°C (rectal temperature) within 48 hours of vaccination, not due to another identifiable cause.
- Collapse or shock-like state 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°C on rectal setting.
Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK2202083A + SYNFLORIX GROUP	Synflorix™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of GSK2202083A and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of GSK2202083A vaccine at Day 0 and of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
GSK2202083A + SYNFLORIX GROUP	GSK2202083A vaccine	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of GSK2202083A and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of GSK2202083A vaccine at Day 0 and of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
INFANRIX HEXA/MENJUGATE GROUP	Infanrix hexa™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and 2 doses of Menjugate® vaccine in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with Menjugate® vaccine at Day 0. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
INFANRIX HEXA/NEISVAC-C + SYNFLORIX GROUP	NeisVac-C™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with NeisVac-C® vaccine at Day 0 and 1 dose of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
INFANRIX HEXA/MENJUGATE GROUP	Menjugate™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and 2 doses of Menjugate® vaccine in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with Menjugate® vaccine at Day 0. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
INFANRIX HEXA/NEISVAC-C + SYNFLORIX GROUP	Infanrix hexa™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with NeisVac-C® vaccine at Day 0 and 1 dose of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.
INFANRIX HEXA/NEISVAC-C + SYNFLORIX GROUP	Synflorix™	Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with NeisVac-C® vaccine at Day 0 and 1 dose of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh.

Primary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects Against Polyribosyl-Ribitol-Phosphate (PRP)	At Month 1, post-booster dose	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).
Number of Seroprotected Subjects Against Neisseria Meningitidis Serogroup C Using Baby Rabbit Completent (rSBA-MenC)	At Month 1, post-booster dose	A seroprotected subject was defined as a subject with anti-rSBA-MenC titers greater than or equal to (≥) 1:8.

Secondary Outcome Measures

Name	Time	Method
Anti-rSBA-MenC Antibody Titres	At Month 0 and Month 1, before and one month after booster dose	Antibody titers were expressed as geometric mean titers (GMTs) for the seroprotection cut-off value of ≥ 1:8.
Number of Seropositive Subjects for Anti-PRP	At Month 0, before the booster dose	A seropositive subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 μg/mL.
Anti-HBs Antibody Concentrations	At Month 0 and Month 1, before and after booster dose	Concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL.
Number of Subjects With Anti-PRP Antibody Concentrations ≥ the Cut-off	At Month 0 and Month 1, before and one month after booster dose	The cut-off value of the assay was an anti-PRP antibody concentration ≥ 1 μg/mL.
Anti-PRP Antibody Concentrations	At Month 0 and Month 1, before and one month after booster dose	Concentrations were expressed as geometric mean concentrations (GMCs) for the cut-off value of ≥ 0.15 μg/mL.
Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)	At Month 0 and Month 1, before and one month after booster dose	A seropositive subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Number of Seroprotected Subjects Against rSBA-MenC	At Month 0, before the booster dose	A seroprotected subject was defined as a subject with anti-rSBA-MenC antibody titers ≥ 1:8.
Number of Seropositive Subjects for Anti-rSBA-MenC	At Month 0 and Month 1, before and one month after booster dose	A seropositive subject for anti-rSBA-MenC was defined as a subject with antibody titers greater than or equal to (≥) 1:128.
Number of Subjects With Polysaccharide N. Meningitidis Serogroup C (PSC) Antibody Concentrations ≥ Cut-off Values	At Month 0 and Month 1, before and one month after booster dose	The cut-off values assessed were ≥ 0.3 μg/mL and ≥ 2 μg/mL.
Anti-PSC Antibody Concentrations	At Month 0 and Month 1, before and one month after booster dose	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.3 μg/mL.
Number of Seropositive Subjects for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T)	At Month 0 and Month 1, before and one month after booster dose	A seropositive subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL).
Number of Subjects With Any Solicited Local Symptoms	During the 8-day (Days 0-7) post-booster period	Solicited local symptoms assessed included pain, redness and swelling. Any= all reports of the speecified symptom irrespective of intensity grade.
Anti-D and Anti-T Antibody Concentrations	At Month 0 and Month 1, before and one month after booster dose	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.1 IU/mL.
Anti-poliovirus Types 1, 2 and 3 Antibody Titres	At Month 0 and Month 1, before and one month after booster dose	Titers were expressed as geometric mean titters (GMTs) for the seropositivity cut-off value of ≥ 1:8.
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	At Month 0 and Month 1, before and one month after booster dose	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value ≥ 5 EL.U/mL.
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 31-day (Days 0-30) post-booster period	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.
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Cut-off Values	At Month 0 and Month 1, before and one month after booster dose	The cut-off values assessed were 3.3 milli-international units per milliliter (mIU/mL), 10 mIU/mL and 100 mIU/mL.
Number of Seropositive Subjects for Anti-poliovirus Types 1, 2 and 3	At Month 0 and Month 1, before and one month after booster dose	A seropositive subject was defined as a subject with anti-polio type 1, 2 or 3 ≥ 1:8.
Number of Subjects With Any Solicited General Symptoms	During the 8-day (Days 0-7) post-booster period	Solicited general symptoms assessed included drowsiness, irritability, loss of appetite and fever (defined as axillary temperature ≥ 37.5º C). Any= all reports of the specified symptom irrespective of intensity grade and relationship to vaccination.
Number of Subjects With Serious Adverse Events (SAEs)	After the booster dose of the study vaccine up to the study end (from Month 0 to Month 1)	SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.