Infections, Streptococcal
Conditions
Keywords
Catch-up vaccination, Pneumococcal vaccine, Immune memory, Nasopharyngeal carriage, Immunogenicity, Pneumococcal disease, Safety
Brief summary
The objective of this study is to evaluate the immune memory through the administration of an additional dose of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A, the antibody persistence and long-term effect on nasopharyngeal carriage of S. pneumoniae and H. influenzae in subjects primed and boosted with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A in previous primary and booster studies. For subjects that did not receive the investigational vaccine during the primary and booster study, the objective is to evaluate immunogenicity, safety and reactogenicity of a 2-dose catch-up vaccination with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A. This protocol posting deals with objectives & outcome measures of the extension phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00370318). The objectives & outcome measures of the booster phase are presented in a separate protocol posting (NCT00496015).
Detailed description
This protocol posting has been updated according to Protocol Amendment 1, July 2009
Interventions
BIOLOGICALPneumococcal vaccine GSK1024850A
1 or 2 intramuscular injections
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
31 Months to 44 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female between, and including, 31 and 34 months of age at the time of the enrolment. * Subjects who previously participated in study NCT00496015 * For the subjects in the primed AP-AP and NAP-pre groups: subjects who received a booster dose of the pneumococcal conjugate vaccine prior to the study amendment 3. * For the subjects in the unprimed group: subjects who received a dose of the meningococcal vaccine GSK134612. * Written informed consent obtained from the parent or guardian of the subject. * Free of obvious health problems 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) other than the study vaccine within 30 days preceding enrolment, or planned use during the entire study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the entire study period. * 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. * 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). * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * History of seizures or progressive neurological disease. * Acute disease at the time of enrolment, defined as the presence of a mild, moderate or severe illness with or without fever. * Administration or planned use of immunoglobulins and/ or any blood products during the entire study period. * A family history of congenital or hereditary immunodeficiency. * Major congenital defects or serious chronic illness. * Subjects of which both parents have a history of atopia (polinosis, asthma, atopic eczema). * Administration of any pneumococcal vaccine since the end of study NCT00496015.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Concentrations Against Vaccine Pneumococcal Serotypes | At 7-10 days after the first vaccine dose | Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Prior to (Day 0) and 7-10 days after the first vaccine dose | Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). |
| Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Prior to (Day 0) and 7-10 days after the first vaccine dose | The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. |
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Prior to (Day 0) and 7-10 days after the first vaccine dose | Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs). |
| Antibody Concentrations Against Protein D (Anti-PD) | Prior to (Day 0) and 7-10 days after the first vaccine dose | Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL. |
| Memory B-cell Detection for Vaccine Polysaccharides (PS) | Prior to (Day 0) and 7-10 days after the first vaccine dose | B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population. |
| Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | At 25-36 months post-vaccination in previous 107137 (NCT00496015) study | The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8. |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | During the 4-day (Days 0-3) post-vaccination period | Assessed solicited local symptoms 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 spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups. |
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | During the 4-day (Days 0-3) post-vaccination period | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that 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 = fever \> 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups. |
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | Within 31 days (Days 0-30) after each vaccination | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Prior to the first study vaccine dose (At Day 0) | Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL. |
| Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded. |
| Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded. |
| Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded. |
| Number of Nasopharyngeal Swabs With Haemophilus Influenzae | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | Positive cultures of H. influenzae identified in the nasopharynx were recorded. |
| Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | The number of subjects with new acquisition of S. pneumoniae (Synflorix™ vaccine serotypes) detected in nasopharyngeal swabs was recorded. |
| Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. |
| Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. |
| Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the entire study period (from Day 0 up to Month 10 or Month 12) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. |
Countries
Czechia
Participant flow
Pre-assignment details
Out of the 466 subjects enrolled in the study, 5 subjects were not included in the Total effective cohort as they did not meet eligibility criteria. Out of the 461 subjects enrolled in the Total effective cohort, 18 subjects were not included in the Total vaccinated cohort as these subjects withdrew before the first vaccination visit (Visit 2).
Participants by arm
| Arm | Count |
|---|---|
| Synflorix I Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol. | 112 |
| Synflorix II Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment. | 108 |
| Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle. | 223 |
| Total | 443 |
Baseline characteristics
| Characteristic | Synflorix I Group | Synflorix II Group | Synflorix III Group | Total |
|---|---|---|---|---|
| Age, Continuous | 39.2 Months STANDARD_DEVIATION 1.53 | 39.1 Months STANDARD_DEVIATION 1.54 | 37.7 Months STANDARD_DEVIATION 3.36 | 38.4 Months STANDARD_DEVIATION 2.71 |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic / North African heritage | 0 Participants | 0 Participants | 9 Participants | 9 Participants |
| Race/Ethnicity, Customized White - Caucasian / European heritage | 111 Participants | 108 Participants | 214 Participants | 433 Participants |
| Sex: Female, Male Female | 60 Participants | 48 Participants | 99 Participants | 207 Participants |
| Sex: Female, Male Male | 52 Participants | 60 Participants | 124 Participants | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 108 | 0 / 223 |
| other Total, other adverse events | 96 / 112 | 86 / 108 | 190 / 223 |
| serious Total, serious adverse events | 0 / 112 | 0 / 108 | 0 / 223 |
Outcome results
Primary
Antibody Concentrations Against Vaccine Pneumococcal Serotypes
Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL.
Time frame: At 7-10 days after the first vaccine dose
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-1 | 1.24 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-4 | 4.52 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.72 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.27 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-7F | 1.37 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-9V | 0.69 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-14 | 1.01 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-18C | 3.25 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-19F | 4.31 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.25 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-18C | 32.54 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-1 | 7.63 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-9V | 9.75 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-4 | 12.95 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-23F | 9.24 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-5 | 9.76 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-14 | 23.07 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-6B | 7.67 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-19F | 39.84 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-7F | 6.51 μg/mL |
Comparison: To demonstrate the immunological memory induced for anti-pneumococcal serotype 1 following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [5.03, 7.58]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 4 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [2.38, 3.45]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 5 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [10.96, 16.55]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 6B induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [22.54, 36.81]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 7F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [3.9, 5.78]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 9V induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [11.21, 17.75]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 14 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [17.51, 30]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 18C induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [7.95, 12.61]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 19F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [7.29, 11.74]ANOVA
Comparison: To demonstrate the immunological memory for anti-pneumococcal serotype 23F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.95% CI: [27.59, 48.34]ANOVA
Secondary
Antibody Concentrations Against Protein D (Anti-PD)
Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL.
Time frame: At Month 12, one month after the second vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against protein D were available after vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Protein D (Anti-PD) | 785.9 EL.U/mL |
Secondary
Antibody Concentrations Against Protein D (Anti-PD)
Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL.
Time frame: Prior to (Day 0) and 7-10 days after the first vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against protein D were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Protein D (Anti-PD) | Anti-PD, D0 | 105.6 EL.U/mL |
| Synflorix III Group | Antibody Concentrations Against Protein D (Anti-PD) | Anti-PD, D7-10 | 374.3 EL.U/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Protein D (Anti-PD) | Anti-PD, D0 | 464.2 EL.U/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Protein D (Anti-PD) | Anti-PD, D7-10 | 2673.7 EL.U/mL |
Secondary
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A
The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Time frame: At Month 12, one month after the second vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-6A | 0.51 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-19A | 1.99 μg/mL |
Secondary
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A
The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Time frame: Prior to (Day 0) and 7-10 days after the first vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-6A, D0 | 0.11 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-6A, D7-10 | 0.2 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-19A, D0 | 0.22 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-19A, D7-10 | 0.65 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-19A, D7-10 | 6.75 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-6A, D0 | 0.39 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-19A, D0 | 0.52 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | Anti-6A, D7-10 | 2.4 μg/mL |
Secondary
Antibody Concentrations Against Vaccine Pneumococcal Serotypes
The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs), expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Time frame: At Month 12, one month after the second vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-1 | 2.33 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-4 | 6.26 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-5 | 2.69 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.84 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-7F | 3.63 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-9V | 1.73 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-14 | 5.21 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-18C | 13.59 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-19F | 11.83 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.99 μg/mL |
Secondary
Antibody Concentrations Against Vaccine Pneumococcal Serotypes
Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL.
Time frame: Prior to the first study vaccine dose (At Day 0)
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-9V | 0.07 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.1 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-14 | 0.28 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-4 | 0.05 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-18C | 0.09 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.1 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-19F | 0.44 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-1 | 0.09 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.08 μg/mL |
| Synflorix III Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-7F | 0.06 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.96 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-1 | 0.27 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-4 | 0.2 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.41 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.8 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-9V | 0.5 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-14 | 1.21 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-18C | 0.65 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-19F | 2.35 μg/mL |
| Pooled Synflorix I+II Group | Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Anti-7F | 0.48 μg/mL |
Secondary
Memory B-cell Detection for Vaccine Polysaccharides (PS)
B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population.
Time frame: Prior to (Day 0) and 7-10 days after the first vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D0 | 288.6 Memory B-cells | Standard Deviation 352.5 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D7-10 | 1056.7 Memory B-cells | Standard Deviation 1334 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D7-10 | 629.1 Memory B-cells | Standard Deviation 773.2 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D0 | 475.9 Memory B-cells | Standard Deviation 682.3 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D0 | 169.7 Memory B-cells | Standard Deviation 415.3 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D0 | 537.7 Memory B-cells | Standard Deviation 641.8 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D0 | 139.4 Memory B-cells | Standard Deviation 214.7 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D7-10 | 3839 Memory B-cells | Standard Deviation 5960.5 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D7-10 | 679.2 Memory B-cells | Standard Deviation 885.8 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D7-10 | 579.8 Memory B-cells | Standard Deviation 632.5 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D7-10 | 233.5 Memory B-cells | Standard Deviation 235.7 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D7-10 | 1488.8 Memory B-cells | Standard Deviation 1584.2 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D0 | 112.6 Memory B-cells | Standard Deviation 176.1 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D0 | 372 Memory B-cells | Standard Deviation 545.5 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D7-10 | 1017.4 Memory B-cells | Standard Deviation 1309.9 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D0 | 269.5 Memory B-cells | Standard Deviation 432.2 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D0 | 462.5 Memory B-cells | Standard Deviation 704.5 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D0 | 141.9 Memory B-cells | Standard Deviation 232.4 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D7-10 | 406.6 Memory B-cells | Standard Deviation 447.8 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D0 | 327.2 Memory B-cells | Standard Deviation 554.4 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D7-10 | 1265.8 Memory B-cells | Standard Deviation 1738.6 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D0 | 530.9 Memory B-cells | Standard Deviation 693.8 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D7-10 | 8308.4 Memory B-cells | Standard Deviation 7166.9 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D0 | 149.1 Memory B-cells | Standard Deviation 194.4 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D7-10 | 1092.4 Memory B-cells | Standard Deviation 1724.3 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D0 | 285 Memory B-cells | Standard Deviation 484.3 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D7-10 | 1123.7 Memory B-cells | Standard Deviation 2095.4 |
| Pooled Synflorix I+II Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D7-10 | 915.5 Memory B-cells | Standard Deviation 1191.3 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D0 | 639.9 Memory B-cells | Standard Deviation 846.5 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D0 | 469.9 Memory B-cells | Standard Deviation 639.2 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D7-10 | 708.2 Memory B-cells | Standard Deviation 1609.4 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D7-10 | 152.6 Memory B-cells | Standard Deviation 231 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D0 | 254.8 Memory B-cells | Standard Deviation 368.4 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D0 | 185.6 Memory B-cells | Standard Deviation 270.1 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 5 PS, D0 | 81.5 Memory B-cells | Standard Deviation 109.2 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | C-PS, D7-10 | 762.6 Memory B-cells | Standard Deviation 1039.4 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D0 | 135.2 Memory B-cells | Standard Deviation 200.6 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 23F PS, D7-10 | 327.9 Memory B-cells | Standard Deviation 470.5 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 18C PS, D7-10 | 2053.8 Memory B-cells | Standard Deviation 2122.2 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 6B PS, D7-10 | 526 Memory B-cells | Standard Deviation 648.6 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 1 PS, D7-10 | 755.9 Memory B-cells | Standard Deviation 1017.4 |
| Synflorix III Group | Memory B-cell Detection for Vaccine Polysaccharides (PS) | 19F PS, D0 | 164.5 Memory B-cells | Standard Deviation 343.4 |
Secondary
Number of Nasopharyngeal Swabs With Haemophilus Influenzae
Positive cultures of H. influenzae identified in the nasopharynx were recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix III Group | Number of Nasopharyngeal Swabs With Haemophilus Influenzae | 31-44 months | 43 Swabs associated to specified bacteria |
| Synflorix III Group | Number of Nasopharyngeal Swabs With Haemophilus Influenzae | 40-48 months | 89 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With Haemophilus Influenzae | 31-44 months | 54 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With Haemophilus Influenzae | 40-48 months | 74 Swabs associated to specified bacteria |
Secondary
Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)
Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix III Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | 31-44 months | 9 Swabs associated to specified bacteria |
| Synflorix III Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | 40-48 months | 19 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | 31-44 months | 13 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | 40-48 months | 18 Swabs associated to specified bacteria |
Secondary
Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)
Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix III Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | 31-44 months | 25 Swabs associated to specified bacteria |
| Synflorix III Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | 40-48 months | 27 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | 31-44 months | 34 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | 40-48 months | 35 Swabs associated to specified bacteria |
Secondary
Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes)
Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix III Group | Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | 31-44 months | 40 Swabs associated to specified bacteria |
| Synflorix III Group | Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | 40-48 months | 46 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | 31-44 months | 21 Swabs associated to specified bacteria |
| Pooled Synflorix I+II Group | Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | 40-48 months | 20 Swabs associated to specified bacteria |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms 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 spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 75 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 7 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 58 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 13 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 43 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 11 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 41 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 67 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 12 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 5 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 11 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 60 Participants |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms 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 spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the unprimed group.
Time frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any pain, D2 | 121 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 redness, D1 | 23 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any pain, D1 | 150 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 pain, D1 | 13 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any redness, D1 | 102 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any swelling, D1 | 78 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 swelling, D1 | 14 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 pain, D2 | 12 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any redness, D2 | 93 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 redness, D2 | 12 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any swelling, D2 | 65 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 swelling, D2 | 3 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any pain, Across doses | 167 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 pain, Across doses | 23 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any redness, Across doses | 127 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 redness, Across doses | 29 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any swelling, Across doses | 101 Participants |
| Synflorix III Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 swelling, Across doses | 16 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that 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 = fever \> 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the unprimed group.
Time frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any drowsiness, D1 | 79 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 drowsiness, D1 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related drowsiness, D1 | 56 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Irritability, D1 | 69 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability, D1 | 2 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related irritability, D1 | 49 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any loss of appetite, D1 | 47 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 loss of appetite, D1 | 5 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related loss of appetite, D1 | 32 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any fever (Axillary), D1 | 23 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fever (Axillary), D1 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related fever, D1 | 15 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any drowsiness, D2 | 60 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 drowsiness, D2 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related drowsiness, D2 | 43 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Irritability, D2 | 59 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability, D2 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related irritability, D2 | 44 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any loss of appetite, D2 | 26 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 loss of appetite, D2 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related loss of appetite, D2 | 16 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any fever (Axillary), D2 | 9 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related loss of appetite, Across doses | 42 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fever (Axillary), D2 | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related fever, D2 | 5 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any drowsiness, Across doses | 102 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 drowsiness, Across doses | 2 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related drowsiness, Across doses | 73 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Irritability, Across doses | 98 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability, Across doses | 3 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related irritability, Across doses | 74 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any loss of appetite, Across doses | 61 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 loss of appetite, Across doses | 6 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any fever (Axillary), Across doses | 30 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fever (Axillary), Across doses | 2 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related fever, Across doses | 19 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that 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 = fever \> 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any drowsiness | 41 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 drowsiness | 0 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related drowsiness | 26 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Irritability | 33 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Irritability | 21 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any loss of appetite | 23 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 loss of appetite | 1 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related loss of appetite | 13 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any fever (Axillary) | 12 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fever (Axillary) | 0 Participants |
| Synflorix III Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related fever | 10 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fever (Axillary) | 1 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any drowsiness | 34 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any loss of appetite | 15 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 drowsiness | 0 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any fever (Axillary) | 8 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related drowsiness | 26 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 loss of appetite | 1 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Irritability | 26 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related fever | 5 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability | 0 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related loss of appetite | 10 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Irritability | 16 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: Within 31 days (Days 0-30) after each vaccination
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix III Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 24 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 29 Participants |
| Synflorix III Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 73 Participants |
Secondary
Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs
The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | 31-44 months | 35 Participants |
| Synflorix III Group | Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | 40-48 months | 70 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | 31-44 months | 49 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | 40-48 months | 50 Participants |
Secondary
Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs
The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | 31-44 months | 9 Participants |
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | 40-48 months | 18 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | 40-48 months | 18 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | 31-44 months | 13 Participants |
Secondary
Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs
The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | 31-44 months | 24 Participants |
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | 40-48 months | 25 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | 31-44 months | 32 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | 40-48 months | 33 Participants |
Secondary
Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs
The number of subjects with new acquisition of S. pneumoniae (Synflorix™ vaccine serotypes) detected in nasopharyngeal swabs was recorded.
Time frame: At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
Population: The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | 31-44 months | 39 Participants |
| Synflorix III Group | Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | 40-48 months | 41 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | 31-44 months | 20 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | 40-48 months | 18 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: During the entire study period (from Day 0 up to Month 10 or Month 12)
Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix III Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
| Pooled Synflorix I+II Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
| Synflorix III Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).
Time frame: Prior to (Day 0) and 7-10 days after the first vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-6A, D0 | 49 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-6A, D7-10 | 863.3 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-19A, D0 | 10.3 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-19A, D7-10 | 880.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-19A, D7-10 | 2104.9 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-6A, D0 | 95.2 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-19A, D0 | 15.9 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-6A, D7-10 | 2408.4 Titers |
Secondary
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).
Time frame: At Month 12, one month after the second vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-6A | 918.6 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Opsono-19A | 597.6 Titers |
Secondary
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F).
Time frame: At Month 12, one month after the second vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-1 | 125.6 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-4 | 2451.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-5 | 57.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-6B | 1345 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-7F | 6527.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-9V | 6091.6 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-14 | 4544.9 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-18C | 3827.5 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-19F | 1251 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-23F | 4629.1 Titers |
Secondary
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F).
Time frame: Prior to (Day 0) and 7-10 days after the first vaccine dose
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-7F, D0 | 973.4 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-1, D0 | 5.4 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-1, D7-10 | 632 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-4, D0 | 9.1 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-4, D7-10 | 13109.9 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-5, D0 | 4 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-5, D7-10 | 145.8 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-6B, D0 | 46.7 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-6B, D7-10 | 1472.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-7F, D7-10 | 13647.4 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-9V, D0 | 268.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-9V, D7-10 | 14668.8 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-14, D0 | 145.3 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-14, D7-10 | 4454.3 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-18C, D0 | 5.7 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-18C, D7-10 | 9092.2 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-19F, D0 | 12.9 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-19F, D7-10 | 902.5 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-23F, D0 | 220.6 Titers |
| Synflorix III Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-23F, D7-10 | 5776.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-19F, D7-10 | 6271.1 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-9V, D0 | 481.8 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-1, D0 | 10.2 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-18C, D7-10 | 7413.8 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-1, D7-10 | 3106.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-9V, D7-10 | 17952.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-4, D0 | 18.1 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-23F, D7-10 | 15613.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-4, D7-10 | 27273.3 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-14, D0 | 267.6 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-5, D0 | 8.9 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-19F, D0 | 79.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-5, D7-10 | 1020 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-14, D7-10 | 16256.8 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-6B, D0 | 163.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-23F, D0 | 462.7 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-6B, D7-10 | 5789.5 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-7F, D0 | 1112.3 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-18C, D0 | 14.2 Titers |
| Pooled Synflorix I+II Group | Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Opsono-7F, D7-10 | 19988.9 Titers |
Secondary
Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men)
The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8.
Time frame: At 25-36 months post-vaccination in previous 107137 (NCT00496015) study
Population: The analysis was performed on the ATP cohort for antibody persistence, which included all subjects with the vaccine administration documented, for whom assay results were available for antibodies against each considered antigen for the blood sample taken before the administration of Synflorix™ vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix III Group | Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | rSBA-MenA | 325.5 Titers |
| Synflorix III Group | Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | rSBA-MenC | 63.6 Titers |
| Synflorix III Group | Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | rSBA-MenY | 372.2 Titers |
| Synflorix III Group | Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | rSBA-MenW-135 | 247.6 Titers |