Infections, Streptococcal
Conditions
Keywords
Pneumococcal disease, Pneumococcal vaccine, Catch-up vaccination, Immunogenicity, Booster vaccination, Safety
Brief summary
The purpose of this trial is to assess the safety, reactogenicity and immunogenicity of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A when administered either as a booster dose or as a two dose catch-up vaccination in the second year of life to the Nigerian subjects previously enrolled in the primary vaccination study NCT00678301. 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 = NCT00678301).
Interventions
BIOLOGICALPneumococcal vaccine GSK1024850A
Intramuscular injection, 1 or 2 doses
BIOLOGICALInfanrixTM
Intramuscular injection, 1dose
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Months to 21 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol. * A male or female, between and including 15-21 months of age at the time of visit 1. * For the Pn-Pn group, subjects who completed the full vaccination course in study NCT00678301. For the Zil-Pn group, subjects who were previously enrolled in the control group of study NCT00678301. * Written informed consent, signed or thumb printed, obtained from the parent(s)/LAR(s) of the subject. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by a witness. * 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)/product(s) within 30 days preceding the first dose of vaccine, or planned use during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. * Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of study vaccine and ending 30 days after. Locally recommended vaccines for example Oral Polio Vaccine or influenza vaccine are always allowed, even if concomitantly administered with the study vaccines, but should be documented in the CRF. * 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. * Administration of any pneumococcal vaccine since the end of study NCT00678301. * Any confirmed or suspected immunosuppressive or immunodeficient condition, since the end of study NCT00678301, based on medical history and physical examination. * Major congenital defects or serious chronic illness. * History of any progressive neurological disorders or seizures. * Acute disease and/or fever at the time of enrolment. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Administration of immunoglobulins and/or any blood products less than 3 months prior to visit 1 or planned use during the study. * Child in care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). | Within 31 days (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group. | Grade 3 symptom = severe symptom that prevented normal activity. Solicited local symptoms assessed were pain, redness and swelling. Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Unsolicited AEs = Any AE 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 was reported as an unsolicited adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. |
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8. |
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8. |
| Concentration of Antibodies Against Protein D (PD). | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | Anti-PD antibodies were determined using an ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EL.U/mL). Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EL.U/mL). |
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Within 4 days (Days 0-3) after vaccination. | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = temperature \>39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination. |
| Number of Subjects Reporting Unsolicited AEs. | Within 31 days (Days 0-30) after vaccination | Unsolicited AEs = Any AE (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 was reported as an unsolicited adverse event. |
| Number of Subjects Reporting Serious Adverse Events (SAEs). | During the entire study period, from the vaccination visit at Day 0 up to the end of the follow-up visit at Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. | 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. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Within 4 days (Days 0-3) after vaccination. | Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events was actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre (mm) |
Countries
Nigeria
Participant flow
Recruitment details
The duration of the study depends on the group allocation. The duration of the study per subject can vary from 1 month (Synflorix/Infanrix primed Group) to 3 months (Synflorix/Infanrix unprimed Group).
Pre-assignment details
Because of an issue with the informed consent of a child, the data of the child, who had a non-related to study medication serious adverse event, are not detailed in this analysis. Data were reanalyzed for the 104 subjects with data available.
Participants by arm
| Arm | Count |
|---|---|
| Synflorix/Infanrix Primed Group Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm. | 68 |
| Synflorix/Infanrix Unprimed Group Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm. | 36 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Synflorix/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group | Total |
|---|---|---|---|
| Age, Continuous | 16.7 Months STANDARD_DEVIATION 1 | 16.4 Months STANDARD_DEVIATION 0.91 | 16.55 Months STANDARD_DEVIATION 0.955 |
| Sex: Female, Male Female | 29 Participants | 17 Participants | 46 Participants |
| Sex: Female, Male Male | 39 Participants | 19 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 68 | 25 / 36 |
| serious Total, serious adverse events | 1 / 68 | 0 / 36 |
Outcome results
Primary
Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited).
Grade 3 symptom = severe symptom that prevented normal activity. Solicited local symptoms assessed were pain, redness and swelling. Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Unsolicited AEs = Any AE 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 was reported as an unsolicited adverse event.
Time frame: Within 31 days (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group.
Population: The Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). | Any symptom | 3 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). | General symptoms | 1 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). | Local symptoms | 2 Participants |
Secondary
Concentration of Antibodies Against Protein D (PD).
Anti-PD antibodies were determined using an ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EL.U/mL). Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EL.U/mL).
Time frame: Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Concentration of Antibodies Against Protein D (PD). | Anti-PD [pre-booster;pre-vacc] | 270.4 EL.U/mL |
| Synflorix/Infanrix Primed Group | Concentration of Antibodies Against Protein D (PD). | Anti-PD [post-booster;post-dose 2] | 2955.3 EL.U/mL |
| Synflorix/Infanrix Unprimed Group | Concentration of Antibodies Against Protein D (PD). | Anti-PD [pre-booster;pre-vacc] | 61.5 EL.U/mL |
| Synflorix/Infanrix Unprimed Group | Concentration of Antibodies Against Protein D (PD). | Anti-PD [post-booster;post-dose 2] | 501.1 EL.U/mL |
Secondary
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes.
Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster;pre-vacc] | 0.19 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [post-booster;post-dose 2] | 0.81 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster;pre-vacc] | 0.24 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [post-booster;post-dose 2] | 1.33 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [post-booster;post-dose 2] | 1.94 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster;pre-vacc] | 0.05 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster;pre-vacc] | 0.09 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [post-booster;post-dose 2] | 0.24 µg/mL |
Secondary
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [pre-booster;pre-vacc] | 0.29 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [post-booster;post-dose 2] | 8.72 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [pre-booster;pre-vacc] | 0.40 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [post-booster;post-dose 2] | 11.03 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [pre-booster;pre-vacc] | 0.49 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [post-booster;post-dose 2] | 10.34 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [pre-booster;pre-vacc] | 0.63 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [post-booster;post-dose 2] | 4.31 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [pre-booster;pre-vacc] | 0.73 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [post-booster;post-dose 2] | 10.30 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [pre-booster;pre-vacc] | 1.04 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [post-booster;post-dose 2] | 11.49 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [pre-booster;pre-vacc] | 1.13 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [post-booster;post-dose 2] | 14.14 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [pre-booster;pre-vacc] | 1.62 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [post-booster;post-dose 2] | 35.33 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [pre-booster;pre-vacc] | 1.20 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [post-booster;post-dose 2] | 9.26 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [pre-booster;pre-vacc] | 0.46 µg/mL |
| Synflorix/Infanrix Primed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [post-booster;post-dose 2] | 6.99 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [post-booster;post-dose 2] | 7.16 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [pre-booster;pre-vacc] | 0.03 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [pre-booster;pre-vacc] | 0.06 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [post-booster;post-dose 2] | 3.17 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [post-booster;post-dose 2] | 25.61 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [pre-booster;pre-vacc] | 0.06 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [post-booster;post-dose 2] | 2.70 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [post-booster;post-dose 2] | 8.22 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [post-booster;post-dose 2] | 1.06 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [pre-booster;pre-vacc] | 0.05 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [pre-booster;pre-vacc] | 0.14 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [post-booster;post-dose 2] | 2.87 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [pre-booster;pre-vacc] | 0.14 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [pre-booster;pre-vacc] | 0.05 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [post-booster;post-dose 2] | 10.59 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [post-booster;post-dose 2] | 0.85 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [pre-booster;pre-vacc] | 0.03 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [pre-booster;pre-vacc] | 0.05 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [pre-booster;pre-vacc] | 0.05 µg/mL |
| Synflorix/Infanrix Unprimed Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [post-booster;post-dose 2] | 6.07 µg/mL |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs.
Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events was actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre (mm)
Time frame: Within 4 days (Days 0-3) after vaccination.
Population: The Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any pain | 27 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Grade 3 pain | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any redness | 1 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Redness > 30 mm | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any swelling | 4 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Swelling > 30 mm | 2 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any swelling | 2 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any pain | 13 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Redness > 30 mm | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Grade 3 pain | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Swelling > 30 mm | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Any redness | 1 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs.
Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = temperature \>39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination.
Time frame: Within 4 days (Days 0-3) after vaccination.
Population: The Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any drowsiness | 2 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 drowsiness | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related drowsiness | 2 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Fever >= 37.5°C | 8 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Fever > 39.5°C | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related fever | 8 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any irritability | 2 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 irritability | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related irritability | 2 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any loss of appetite | 1 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 loss of appetite | 0 Participants |
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related loss of appetite | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 loss of appetite | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any drowsiness | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any irritability | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 drowsiness | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Any loss of appetite | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related drowsiness | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Grade 3 irritability | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Fever >= 37.5°C | 3 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related loss of appetite | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Fever > 39.5°C | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related irritability | 0 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. | Related fever | 3 Participants |
Secondary
Number of Subjects Reporting 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.
Time frame: During the entire study period, from the vaccination visit at Day 0 up to the end of the follow-up visit at Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group.
Population: The Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 1 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 0 Participants |
Secondary
Number of Subjects Reporting Unsolicited AEs.
Unsolicited AEs = Any AE (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 was reported as an unsolicited adverse event.
Time frame: Within 31 days (Days 0-30) after vaccination
Population: The Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix/Infanrix Primed Group | Number of Subjects Reporting Unsolicited AEs. | 31 Participants |
| Synflorix/Infanrix Unprimed Group | Number of Subjects Reporting Unsolicited AEs. | 18 Participants |
Secondary
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes.
Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8.
Time frame: One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | Opsono-6A [post-booster;post-dose 2] | 213.0 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | Opsono-19A [post-booster;post-dose 2] | 112.7 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | Opsono-6A [post-booster;post-dose 2] | 313.9 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | Opsono-19A [post-booster;post-dose 2] | 341.2 Titres |
Secondary
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes.
Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8.
Time frame: One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-1 [post-booster;post-dose 2] | 1667.8 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-4 [post-booster;post-dose 2] | 3869.1 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-5 [post-booster;post-dose 2] | 679.9 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-6B [post-booster;post-dose 2] | 1687.6 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-7F [post-booster;post-dose 2] | 11045.3 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-9V [post-booster;post-dose 2] | 5300.1 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-14 [post-booster;post-dose 2] | 2472.0 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-18C [post-booster;post-dose 2] | 2323.0 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-19F [post-booster;post-dose 2] | 683.5 Titres |
| Synflorix/Infanrix Primed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-23F [post-booster;post-dose 2] | 5144.5 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-18C [post-booster;post-dose 2] | 4104.2 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-1 [post-booster;post-dose 2] | 103.4 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-9V [post-booster;post-dose 2] | 6375.3 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-4 [post-booster;post-dose 2] | 1482.9 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-23F [post-booster;post-dose 2] | 3081.7 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-5 [post-booster;post-dose 2] | 58.7 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-14 [post-booster;post-dose 2] | 1797.8 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-6B [post-booster;post-dose 2] | 325.7 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-19F [post-booster;post-dose 2] | 443.5 Titres |
| Synflorix/Infanrix Unprimed Group | Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsono-7F [post-booster;post-dose 2] | 7980.2 Titres |