Trial Outcomes & Findings for Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Mali (NCT NCT00985465)

Last Updated: 2018-12-14

Results Overview

The incidence and nature of Grade 3 symptoms (solicited and unsolicited), reported during the 31-day (Days 0-30) post-vaccination are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

218 participants

Primary outcome timeframe

Within 31 days (Day 0-Day 30) after booster vaccination

Results posted on

2018-12-14

Participant Flow

A total of 218 subjects were enrolled (147 subjects in the Synflorix Primed Group and 71 subjects in the Synflorix Unprimed Group). A total of 210 subjects were vaccinated in the booster vaccination study (141 out of 160 from the Synflorix Primed Group and 69 out of 78 from the Synflorix Unprimed Group).

Participant milestones

Participant milestones
Measure	Synflorix Primed Group Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).
Overall Study STARTED	141	69
Overall Study COMPLETED	140	66
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Synflorix Primed Group Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).
Overall Study Withdrawal by Subject	1	2
Overall Study Considered to be part of the other group	0	1

Baseline Characteristics

Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Mali

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).	Synflorix Unprimed Group n=69 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Total n=210 Participants Total of all reporting groups
Age, Continuous	17 Months STANDARD_DEVIATION 1.11 • n=5 Participants	16.9 Months STANDARD_DEVIATION 1.16 • n=7 Participants	16.97 Months STANDARD_DEVIATION 1.12 • n=5 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	35 Participants n=7 Participants	110 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	34 Participants n=7 Participants	100 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 31 days (Day 0-Day 30) after booster vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

The incidence and nature of Grade 3 symptoms (solicited and unsolicited), reported during the 31-day (Days 0-30) post-vaccination are presented.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Grade 3 Adverse Events (Solicited and Unsolicited) Any symptom	—	3 Participants
Number of Subjects With Grade 3 Adverse Events (Solicited and Unsolicited) General symptoms	—	1 Participants
Number of Subjects With Grade 3 Adverse Events (Solicited and Unsolicited) Local symptoms	—	2 Participants

SECONDARY outcome

Timeframe: Within 4 days (Day 0-Day 3) after the booster dose

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Pain	—	40 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Pain	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Redness	—	17 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Redness	—	2 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Swelling	—	67 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling	—	0 Participants

SECONDARY outcome

Timeframe: Within 4 days (Day 0-Day 3) after the booster dose

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

Assessed solicited general symptoms were drowsiness, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Drowsiness and Irritability = symptom that 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 related to the vaccination.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Drowsiness	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Drowsiness	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Drowsiness	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Fever	—	34 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Fever	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Fever	—	31 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability	—	8 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Irritability	—	8 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Loss of appetite	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Loss of appetite	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Loss of appetite	—	1 Participants

SECONDARY outcome

Timeframe: Within 4 days (Day 0-Day 3) after each vaccine dose

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=69 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Pain, Dose 1	—	22 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Pain, Dose 1	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Redness, Dose 1	—	6 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Redness, Dose 1	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Swelling, Dose 1	—	46 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling, Dose 1	—	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Pain, Dose 2	—	7 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Pain, Dose 2	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Redness, Dose 2	—	2 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Redness, Dose 2	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Swelling, Dose 2	—	31 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling, Dose 2	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Pain, Across Doses	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Redness, Across Doses	—	8 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Redness, Across Doses	—	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Swelling, Across Doses	—	55 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling, Across Doses	—	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Pain, Across Doses	—	25 Participants

SECONDARY outcome

Timeframe: Within 4 days (Day 0-Day 3) after each vaccine dose

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=69 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Drowsiness, Dose 1	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Drowsiness, Dose 1	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Drowsiness, Dose 1	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Fever, Dose 1	—	21 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Fever, Dose 1	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Fever, Dose 1	—	19 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, Dose 1	—	3 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, Dose 1	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Irritability, Dose 1	—	3 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Loss of appetite, Dose 1	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Loss of appetite, Dose 1	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Loss of appetite, Dose 1	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Drowsiness, Dose 2	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Drowsiness, Dose 2	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Drowsiness, Dose 2	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Fever, Dose 2	—	17 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Fever, Dose 2	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Fever, Dose 2	—	15 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, Dose 2	—	3 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, Dose 2	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Irritability, Dose 2	—	3 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Loss of appetite, Dose 2	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Loss of appetite, Dose 2	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Loss of appetite, Dose 2	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Drowsiness, Across Doses	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Drowsiness, Across Doses	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Drowsiness, Across Doses	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Fever, Across Doses	—	34 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Fever, Across Doses	—	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Fever, Across Doses	—	30 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, Across Doses	—	6 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, Across Doses	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Irritability, Across Doses	—	6 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Loss of appetite, Across Doses	—	2 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Loss of appetite, Across Doses	—	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Loss of appetite, Across Doses	—	1 Participants

SECONDARY outcome

Timeframe: Within 31 days (Day 0-Day 30) after each vaccine dose

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

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.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=69 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Any Unsolicited Adverse Events (AEs)	57 Participants	95 Participants

SECONDARY outcome

Timeframe: From the first vaccination up to one month (31 days) after the last vaccination for each subject

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

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.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=69 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=141 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Number of Subjects With Serious Adverse Events (SAEs)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Prior to (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom immunogenicity data were available.

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 milliliter (μg/mL). Pneumococcal serotype specific total immunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was ≥ 0.05 μg/mL.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=59 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=140 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-1, PRE	0.04 μg/mL Interval 0.03 to 0.05	0.28 μg/mL Interval 0.23 to 0.35
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-1, POST	3.2 μg/mL Interval 2.68 to 3.84	5.85 μg/mL Interval 5.07 to 6.76
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-4, PRE	0.06 μg/mL Interval 0.04 to 0.09	0.32 μg/mL Interval 0.26 to 0.38
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-4, POST	6.54 μg/mL Interval 5.47 to 7.82	10.44 μg/mL Interval 9.31 to 11.71
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-5, PRE	0.04 μg/mL Interval 0.03 to 0.05	0.37 μg/mL Interval 0.32 to 0.43
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-5, POST	3.05 μg/mL Interval 2.4 to 3.87	6.07 μg/mL Interval 5.2 to 7.1
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-6B, PRE	0.03 μg/mL Interval 0.03 to 0.04	0.66 μg/mL Interval 0.55 to 0.8
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-6B, POST	0.78 μg/mL Interval 0.57 to 1.08	4.44 μg/mL Interval 3.69 to 5.33
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-7F, PRE	0.04 μg/mL Interval 0.03 to 0.06	0.68 μg/mL Interval 0.59 to 0.8
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-7F, POST	4.5 μg/mL Interval 3.8 to 5.33	7.82 μg/mL Interval 6.92 to 8.85
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-9V, PRE	0.03 μg/mL Interval 0.03 to 0.04	0.73 μg/mL Interval 0.61 to 0.87
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-9V, POST	1.48 μg/mL Interval 1.2 to 1.83	7.99 μg/mL Interval 6.86 to 9.3
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-14, PRE	0.11 μg/mL Interval 0.09 to 0.14	0.9 μg/mL Interval 0.73 to 1.09
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-14, POST	4.51 μg/mL Interval 3.63 to 5.61	9.75 μg/mL Interval 8.02 to 11.85
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-18C, PRE	0.05 μg/mL Interval 0.04 to 0.07	0.92 μg/mL Interval 0.79 to 1.07
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-18C, POST	10.95 μg/mL Interval 8.5 to 14.1	23.99 μg/mL Interval 20.29 to 28.37
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-19F, PRE	0.09 μg/mL Interval 0.06 to 0.14	0.82 μg/mL Interval 0.66 to 1.04
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-19F, POST	8.52 μg/mL Interval 5.58 to 13.0	12.96 μg/mL Interval 10.96 to 15.34
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-23F, PRE	0.03 μg/mL Interval 0.03 to 0.04	0.35 μg/mL Interval 0.28 to 0.45
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Anti-23F, POST	1.05 μg/mL Interval 0.74 to 1.49	4.25 μg/mL Interval 3.54 to 5.11

SECONDARY outcome

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom immunogenicity data were available.

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=58 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=139 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-1, PRE	5.8 Titers Interval 4.3 to 7.8	9.3 Titers Interval 7.3 to 11.8
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-1, POST	108.7 Titers Interval 79.5 to 148.6	661.7 Titers Interval 513.5 to 852.6
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-4, PRE	11.8 Titers Interval 6.3 to 22.1	24 Titers Interval 16.7 to 34.6
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-4, POST	2716.7 Titers Interval 2149.0 to 3434.2	6541.7 Titers Interval 5468.5 to 7825.6
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-5, PRE	4.3 Titers Interval 3.7 to 5.0	9 Titers Interval 7.4 to 10.9
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-5, POST	71.9 Titers Interval 51.8 to 99.7	340.5 Titers Interval 272.2 to 426.0
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-6B, PRE	38.7 Titers Interval 16.2 to 92.0	82.6 Titers Interval 50.5 to 135.1
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-6B, POST	1202.9 Titers Interval 701.3 to 2063.0	1729 Titers Interval 1361.9 to 2194.9
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-7F, PRE	2454.4 Titers Interval 1587.3 to 3795.1	3230.6 Titers Interval 2588.4 to 4032.1
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-7F, POST	9161.1 Titers Interval 7254.1 to 11569.4	9116.9 Titers Interval 7679.8 to 10822.9
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-9V, PRE	138.2 Titers Interval 63.2 to 302.6	407.9 Titers Interval 265.3 to 627.0
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-9V, POST	4596.5 Titers Interval 3519.4 to 6003.3	3640.4 Titers Interval 2859.0 to 4635.3
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-14, PRE	18.8 Titers Interval 8.4 to 42.3	84.3 Titers Interval 53.4 to 132.9
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-14, POST	2246.1 Titers Interval 1621.5 to 3111.1	3281.8 Titers Interval 2488.4 to 4328.2
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-18C, PRE	6.4 Titers Interval 4.0 to 10.3	6 Titers Interval 4.8 to 7.5
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-18C, POST	2045.3 Titers Interval 1161.5 to 3601.8	2413.2 Titers Interval 1925.5 to 3024.6
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-19F, PRE	4.8 Titers Interval 3.7 to 6.3	12.8 Titers Interval 9.3 to 17.7
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-19F, POST	693.7 Titers Interval 350.8 to 1371.6	1084.2 Titers Interval 828.9 to 1418.1
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-23F, PRE	30.4 Titers Interval 12.9 to 71.4	90.7 Titers Interval 52.7 to 156.2
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Opsono-23F, POST	3571 Titers Interval 2793.4 to 4565.1	3476.4 Titers Interval 2706.8 to 4464.7

SECONDARY outcome

Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (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.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=59 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=140 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-6A, PRE	0.04 μg/mL Interval 0.03 to 0.05	0.13 μg/mL Interval 0.11 to 0.17
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-6A, POST	0.1 μg/mL Interval 0.07 to 0.14	0.55 μg/mL Interval 0.42 to 0.73
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-19A, PRE	0.06 μg/mL Interval 0.04 to 0.09	0.16 μg/mL Interval 0.13 to 0.22
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-19A, POST	1.36 μg/mL Interval 0.91 to 2.03	1.13 μg/mL Interval 0.83 to 1.53

SECONDARY outcome

OPA titers against pneumococcal serotypes 6A and 19A (Opsono-6A and Opsono-19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=58 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=138 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-6A, PRE	24 Titers Interval 12.5 to 46.3	18.7 Titers Interval 12.2 to 28.6
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-6A, POST	106.3 Titers Interval 46.3 to 244.0	100.7 Titers Interval 60.4 to 168.0
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-19A, PRE	5.9 Titers Interval 4.2 to 8.3	6.2 Titers Interval 5.1 to 7.6
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-19A, POST	171.2 Titers Interval 94.2 to 311.3	91.5 Titers Interval 60.4 to 138.5

SECONDARY outcome

Concentrations of antibodies against protein D (PD) were determined by ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (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 milliliter (EL.U/mL).

Outcome measures

Outcome measures
Measure	Synflorix Unprimed Group n=59 Participants Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).	Synflorix Primed Group n=139 Participants Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).
Concentrations of Antibodies Against Protein D (PD) Anti-PD, PRE	62.1 EL.U/mL Interval 54.9 to 70.3	301.1 EL.U/mL Interval 257.7 to 351.8
Concentrations of Antibodies Against Protein D (PD) Anti-PD, POST	839.3 EL.U/mL Interval 643.5 to 1094.6	3710.1 EL.U/mL Interval 3109.0 to 4427.4

Adverse Events

Synflorix Primed Group

Serious events: 0 serious events

Other events: 125 other events

Deaths: 0 deaths

Synflorix Unprimed Group

Serious events: 0 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Synflorix Primed Group n=141 participants at risk Subjects who were previously primed with the Synflorix™ vaccine in study 10PN-PD-DIT-032, received a booster dose of the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, at 15-21 months of age (Study Month 0).	Synflorix Unprimed Group n=69 participants at risk Unprimed subjects from the control group of study 10PN-PD-DIT-032, received a two dose catch-up vaccination with the Synflorix™ vaccine, administered intramuscularly in the thigh or deltoid, during the second year of life (at 15-21 months of age \[Study Month 0\] and at 17-23 months of age \[Study Month 2\]).
Injury, poisoning and procedural complications Wound	0.71% 1/141 • Number of events 1 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	8.7% 6/69 • Number of events 6 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Respiratory, thoracic and mediastinal disorders Allergic bronchitis	27.0% 38/141 • Number of events 41 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	31.9% 22/69 • Number of events 25 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Surgical and medical procedures Circumcision	0.71% 1/141 • Number of events 1 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	5.8% 4/69 • Number of events 4 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Gastrointestinal disorders Enteritis	4.3% 6/141 • Number of events 6 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	11.6% 8/69 • Number of events 10 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Skin and subcutaneous tissue disorders Erythema	12.1% 17/141 • Number of events 17 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	11.6% 8/69 • Number of events 8 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Infections and infestations Gastroenteritis	8.5% 12/141 • Number of events 12 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	21.7% 15/69 • Number of events 16 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
General disorders Injection site induration	3.5% 5/141 • Number of events 5 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	14.5% 10/69 • Number of events 10 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Psychiatric disorders Irritability	5.7% 8/141 • Number of events 8 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	8.7% 6/69 • Number of events 6 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
General disorders Pain	28.4% 40/141 • Number of events 40 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	36.2% 25/69 • Number of events 29 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
General disorders Pyrexia	24.1% 34/141 • Number of events 35 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	49.3% 34/69 • Number of events 38 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Infections and infestations Rhinitis	18.4% 26/141 • Number of events 27 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	20.3% 14/69 • Number of events 15 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
Infections and infestations Skin infection	6.4% 9/141 • Number of events 9 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	4.3% 3/69 • Number of events 3 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.
General disorders Swelling	47.5% 67/141 • Number of events 67 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.	79.7% 55/69 • Number of events 77 • Solicited AEs: within 4 days (Day 0-Day 3) after each vaccine dose; Unsolicited AEs: within 31 days (Day 0-Day 30) after each vaccine dose; SAEs: from the first vaccination up to one month (31 days) after the last vaccination for each subject.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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