Infections, Streptococcal
Conditions
Keywords
Safety, Pneumococcal vaccine, Immunogenicity, Pneumococcal disease, Booster vaccination
Brief summary
The purpose of this study is to evaluate the reactogenicity, safety and immunogenicity of a booster (fourth) dose of pneumococcal vaccine GSK1024850A when co-administered with Hiberix at 12-18 months of age, in children primed with the same vaccines in primary study NCT00680914.
Interventions
BIOLOGICALGSK Biologicals' Synflorix™ (Pneumococcal vaccine GSK1024850A)
Intramuscular injection, administered as a single dose
BIOLOGICALWyeth-Lederle's Prevenar™
Intramuscular injection, administered as a single dose
BIOLOGICALGSK Biologicals' Hiberix™
Intramuscular injection, administered as a single dose
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
12 Months to 18 Months
Healthy volunteers
Yes
Inclusion criteria
* A male or female between, and including, 12-18 months of age at the time of booster vaccination. * Subjects for whom the investigator believes that their parent(s)/ guardian(s) can and will comply with the requirements of the protocol. * Subjects who received three doses of pneumococcal conjugate vaccine in study NCT00680914. * Written informed consent obtained from the parent(s)/guardian(s) of the child/ward. * 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 (drug or vaccine) within 30 days preceding the vaccination, or planned use 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 (pharmaceutical product or device). * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. * Administration of immunoglobulins and/or any blood products within three months preceding the vaccination or planned administration during the study period. * Administration of any pneumococcal and/or Hib vaccine since the end of study NCT00680914. * Planned administration/administration of a vaccine not allowed by the study protocol during the period starting 1 month (30 days) before the administration of the booster dose of the study vaccines (Visit 1) and up to the follow-up visit (Visit 2) with the exception of vaccines included in the Korean routine immunization which can be given at least one week before the administration of the study vaccines or after study end. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * History of reactions or allergic disease likely to be exacerbated by any component of the study vaccines. * Known hypersensitivity to any component of the study vaccines including anaphylactic reactions following the administration of the study vaccines. * Major congenital defects or serious chronic illness. * History of any neurologic disorders or seizures. * Tympanic or axillary/ oral temperature \>= 37.5°C or rectal temperature \>= 38.0°C. A temperature greater than or equal to these cut-offs warrants deferral of the vaccination pending recovery of the subject. * Acute disease at the time of enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Grade 3 Adverse Events | Within 31 days (Day 0 - Day 30) after booster vaccination. | Grade 3 adverse events are severe symptoms that prevent normal, everyday activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Unsolicited Adverse Events | Within 31 days (Days 0 to 30) after booster vaccination | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. |
| Number of Subjects Reporting Serious Adverse Events | After booster vaccination up to study end (Month 0 to Month 1) | Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | One month after booster vaccination (Month 1) | Concentrations of antibodies are measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations expressed as microgram per milliliter (ug/mL). Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. |
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | One month after booster vaccination (Month 1) | Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. |
| Number of Subjects Reporting Solicited Symptoms | Within 4 days (Days 0 to 3) after booster vaccination | Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, fever (equal to or above 37.5 degrees Celsius), irritability and loss of appetite. |
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | One month after booster vaccination (Month 1) | Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. |
| Concentration of Antibodies Against Protein D (PD) | One month after booster vaccination (Month 1) | Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per milliliter (EU/mL). |
| Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) | One month after booster vaccination (Month 1) | Concentrations of antibodies are presented as geometric mean concentrations expressed as microgram per milliliter. |
| Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | One month after booster vaccination (Month 1) | Concentrations of antibodies are measured by 22F-inhibition ELISA and are presented as geometric mean concentrations expressed as microgram per milliliter. |
Countries
South Korea
Participant flow
Pre-assignment details
Two subjects enrolled in the protocol received commercial Prevenar and Hiberix vaccines instead of the clinical vaccines planned to be injected and are as such not included in the number of started subjects below.
Participants by arm
| Arm | Count |
|---|---|
| Synflorix Group Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively. | 335 |
| Prevenar Group Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively. | 113 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 16 | 5 |
Baseline characteristics
| Characteristic | Synflorix Group | Prevenar Group | Total |
|---|---|---|---|
| Age, Continuous | 13.6 months STANDARD_DEVIATION 1.07 | 13.7 months STANDARD_DEVIATION 1 | 13.6 months STANDARD_DEVIATION 1.05 |
| Sex: Female, Male Female | 168 Participants | 59 Participants | 227 Participants |
| Sex: Female, Male Male | 167 Participants | 54 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 243 / 335 | 82 / 113 |
| serious Total, serious adverse events | 8 / 335 | 4 / 113 |
Outcome results
Primary
Number of Subjects Reporting Grade 3 Adverse Events
Grade 3 adverse events are severe symptoms that prevent normal, everyday activities.
Time frame: Within 31 days (Day 0 - Day 30) after booster vaccination.
Population: Analysis was performed on the Total vaccinated cohort on the subjects with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix Group | Number of Subjects Reporting Grade 3 Adverse Events | 42 Participants |
| Prevenar Group | Number of Subjects Reporting Grade 3 Adverse Events | 13 Participants |
Secondary
Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A
Concentrations of antibodies are measured by 22F-inhibition ELISA and are presented as geometric mean concentrations expressed as microgram per milliliter.
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Group | Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Anti-6A | 0.99 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Anti-19A | 1.54 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Anti-6A | 2.51 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Anti-19A | 0.32 ug/mL |
Secondary
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP)
Concentrations of antibodies are presented as geometric mean concentrations expressed as microgram per milliliter.
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Group | Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) | 152.970 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) | 99.738 ug/mL |
Secondary
Concentration of Antibodies Against Protein D (PD)
Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per milliliter (EU/mL).
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Group | Concentration of Antibodies Against Protein D (PD) | 1288.9 EU/mL |
| Prevenar Group | Concentration of Antibodies Against Protein D (PD) | 92.0 EU/mL |
Secondary
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes
Concentrations of antibodies are measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations expressed as microgram per milliliter (ug/mL). Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 4.03 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 5.77 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 5.51 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 2.78 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 5.39 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 4.99 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 7.73 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 13.14 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 16.89 ug/mL |
| Synflorix Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 3.75 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 14.53 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 0.06 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 12.72 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 12.19 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 14.81 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.19 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 22.22 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 7.09 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 4.82 ug/mL |
| Prevenar Group | Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 0.06 ug/mL |
Secondary
Number of Subjects Reporting Serious Adverse Events
Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: After booster vaccination up to study end (Month 0 to Month 1)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix Group | Number of Subjects Reporting Serious Adverse Events | 8 Participants |
| Prevenar Group | Number of Subjects Reporting Serious Adverse Events | 4 Participants |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, fever (equal to or above 37.5 degrees Celsius), irritability and loss of appetite.
Time frame: Within 4 days (Days 0 to 3) after booster vaccination
Population: Analysis was performed on the Total vaccinated cohort on the subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Drowsiness | 75 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Pain | 120 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Fever | 46 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 97 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 141 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 71 Participants |
| Synflorix Group | Number of Subjects Reporting Solicited Symptoms | Redness | 142 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 29 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Pain | 39 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Redness | 55 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 35 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Drowsiness | 21 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Fever | 20 Participants |
| Prevenar Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 42 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
Time frame: Within 31 days (Days 0 to 30) after booster vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix Group | Number of Subjects Reporting Unsolicited Adverse Events | 118 Participants |
| Prevenar Group | Number of Subjects Reporting Unsolicited Adverse Events | 41 Participants |
Secondary
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A
Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions.
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Opsono-6A | 196.1 titer |
| Synflorix Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Opsono-19A | 64.9 titer |
| Prevenar Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Opsono-6A | 1415.7 titer |
| Prevenar Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Opsono-19A | 15.5 titer |
Secondary
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes
Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after booster vaccination (Month 1)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-1 | 363.7 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-4 | 1058.0 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-5 | 233.9 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-6B | 546.5 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-7F | 5467.5 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-9V | 1707.5 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-14 | 1814.6 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-18C | 607.9 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-19F | 1284.5 titer |
| Synflorix Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-23F | 2702.9 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-18C | 1723.3 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-1 | 4.7 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-9V | 5204.0 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-4 | 3717.0 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-23F | 29918.6 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-5 | 4.0 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-14 | 3958.4 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-6B | 3826.8 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-19F | 277.3 titer |
| Prevenar Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-7F | 1038.2 titer |