Trial Outcomes & Findings for Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Nigeria (NCT NCT01153893)

Last Updated: 2018-09-20

Results Overview

Grade 3 symptom = severe symptom that prevented normal activity. Solicited local symptoms assessed were pain, redness and swelling. Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Unsolicited AEs = Any AE reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

105 participants

Primary outcome timeframe

Within 31 days (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group.

Results posted on

2018-09-20

Participant Flow

The duration of the study depends on the group allocation. The duration of the study per subject can vary from 1 month (Synflorix/Infanrix primed Group) to 3 months (Synflorix/Infanrix unprimed Group).

Because of an issue with the informed consent of a child, the data of the child, who had a non-related to study medication serious adverse event, are not detailed in this analysis. Data were reanalyzed for the 104 subjects with data available.

Participant milestones

Participant milestones
Measure	Synflorix/Infanrix Primed Group Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Overall Study STARTED	68	36
Overall Study COMPLETED	67	36
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Synflorix/Infanrix Primed Group Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Overall Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Total n=104 Participants Total of all reporting groups
Age, Continuous	16.7 Months STANDARD_DEVIATION 1.00 • n=5 Participants	16.4 Months STANDARD_DEVIATION 0.91 • n=7 Participants	16.55 Months STANDARD_DEVIATION 0.955 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	17 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	19 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 31 days (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group.

Population: The Total Vaccinated cohort included all vaccinated subjects.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). Any symptom	3 Participants	—
Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). General symptoms	1 Participants	—
Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). Local symptoms	2 Participants	—

SECONDARY outcome

Timeframe: Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group

Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for the blood sample taken one month after vaccination.

Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=35 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-1 [pre-booster;pre-vacc]	0.29 µg/mL Interval 0.22 to 0.4	0.03 µg/mL Interval 0.03 to 0.04
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-1 [post-booster;post-dose 2]	8.72 µg/mL Interval 6.37 to 11.93	3.17 µg/mL Interval 2.58 to 3.89
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-4 [pre-booster;pre-vacc]	0.40 µg/mL Interval 0.31 to 0.5	0.06 µg/mL Interval 0.04 to 0.09
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-4 [post-booster;post-dose 2]	11.03 µg/mL Interval 9.06 to 13.42	8.22 µg/mL Interval 6.75 to 10.02
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-5 [pre-booster;pre-vacc]	0.49 µg/mL Interval 0.4 to 0.61	0.05 µg/mL Interval 0.04 to 0.07
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-5 [post-booster;post-dose 2]	10.34 µg/mL Interval 8.32 to 12.85	2.87 µg/mL Interval 2.22 to 3.71
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-6B [pre-booster;pre-vacc]	0.63 µg/mL Interval 0.48 to 0.83	0.05 µg/mL Interval 0.03 to 0.08
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-6B [post-booster;post-dose 2]	4.31 µg/mL Interval 3.37 to 5.52	0.85 µg/mL Interval 0.52 to 1.38
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-7F [pre-booster;pre-vacc]	0.73 µg/mL Interval 0.57 to 0.92	0.05 µg/mL Interval 0.04 to 0.08
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-7F [post-booster;post-dose 2]	10.30 µg/mL Interval 8.57 to 12.38	6.07 µg/mL Interval 4.89 to 7.52
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-9V [pre-booster;pre-vacc]	1.04 µg/mL Interval 0.78 to 1.39	0.06 µg/mL Interval 0.04 to 0.1
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-9V [post-booster;post-dose 2]	11.49 µg/mL Interval 9.02 to 14.65	2.70 µg/mL Interval 2.05 to 3.55
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-14 [pre-booster;pre-vacc]	1.13 µg/mL Interval 0.87 to 1.46	0.14 µg/mL Interval 0.08 to 0.23
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-14 [post-booster;post-dose 2]	14.14 µg/mL Interval 11.74 to 17.04	10.59 µg/mL Interval 8.7 to 12.89
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-18C [pre-booster;pre-vacc]	1.62 µg/mL Interval 1.3 to 2.04	0.05 µg/mL Interval 0.03 to 0.09
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-18C [post-booster;post-dose 2]	35.33 µg/mL Interval 27.73 to 45.02	25.61 µg/mL Interval 19.7 to 33.3
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-19F [pre-booster;pre-vacc]	1.20 µg/mL Interval 0.85 to 1.71	0.14 µg/mL Interval 0.08 to 0.24
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-19F [post-booster;post-dose 2]	9.26 µg/mL Interval 7.2 to 11.91	7.16 µg/mL Interval 4.27 to 12.02
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-23F [pre-booster;pre-vacc]	0.46 µg/mL Interval 0.32 to 0.68	0.03 µg/mL Interval 0.02 to 0.04
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. Anti-23F [post-booster;post-dose 2]	6.99 µg/mL Interval 5.21 to 9.39	1.06 µg/mL Interval 0.66 to 1.7

SECONDARY outcome

Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=35 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. Anti-6A [pre-booster;pre-vacc]	0.19 µg/mL Interval 0.13 to 0.27	0.05 µg/mL Interval 0.03 to 0.07
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. Anti-6A [post-booster;post-dose 2]	0.81 µg/mL Interval 0.56 to 1.18	0.24 µg/mL Interval 0.15 to 0.4
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. Anti-19A [pre-booster;pre-vacc]	0.24 µg/mL Interval 0.17 to 0.36	0.09 µg/mL Interval 0.05 to 0.17
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. Anti-19A [post-booster;post-dose 2]	1.33 µg/mL Interval 0.88 to 2.0	1.94 µg/mL Interval 1.13 to 3.33

SECONDARY outcome

Timeframe: One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group

Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=67 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=35 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-1 [post-booster;post-dose 2]	1667.8 Titres Interval 1210.9 to 2297.0	103.4 Titres Interval 67.7 to 157.9
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-4 [post-booster;post-dose 2]	3869.1 Titres Interval 3122.8 to 4793.9	1482.9 Titres Interval 1211.0 to 1815.8
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-5 [post-booster;post-dose 2]	679.9 Titres Interval 515.9 to 895.9	58.7 Titres Interval 38.6 to 89.4
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-6B [post-booster;post-dose 2]	1687.6 Titres Interval 1138.7 to 2501.0	325.7 Titres Interval 118.1 to 898.6
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-7F [post-booster;post-dose 2]	11045.3 Titres Interval 8456.8 to 14426.3	7980.2 Titres Interval 6287.8 to 10128.1
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-9V [post-booster;post-dose 2]	5300.1 Titres Interval 4329.3 to 6488.5	6375.3 Titres Interval 4779.4 to 8504.1
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-14 [post-booster;post-dose 2]	2472.0 Titres Interval 1767.3 to 3457.8	1797.8 Titres Interval 1241.4 to 2603.6
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-18C [post-booster;post-dose 2]	2323.0 Titres Interval 1403.1 to 3846.1	4104.2 Titres Interval 2954.5 to 5701.2
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-19F [post-booster;post-dose 2]	683.5 Titres Interval 440.0 to 1062.0	443.5 Titres Interval 203.0 to 968.8
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. Opsono-23F [post-booster;post-dose 2]	5144.5 Titres Interval 3657.4 to 7236.3	3081.7 Titres Interval 1389.3 to 6836.1

SECONDARY outcome

Timeframe: One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group

Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=66 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=35 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. Opsono-6A [post-booster;post-dose 2]	213.0 Titres Interval 121.7 to 372.9	313.9 Titres Interval 147.6 to 667.4
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. Opsono-19A [post-booster;post-dose 2]	112.7 Titres Interval 66.7 to 190.5	341.2 Titres Interval 159.0 to 732.1

SECONDARY outcome

Anti-PD antibodies were determined using an ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EL.U/mL). Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EL.U/mL).

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=67 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=35 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Concentration of Antibodies Against Protein D (PD). Anti-PD [pre-booster;pre-vacc]	270.4 EL.U/mL Interval 211.7 to 345.3	61.5 EL.U/mL Interval 52.0 to 72.7
Concentration of Antibodies Against Protein D (PD). Anti-PD [post-booster;post-dose 2]	2955.3 EL.U/mL Interval 2342.0 to 3729.2	501.1 EL.U/mL Interval 345.0 to 727.9

SECONDARY outcome

Timeframe: Within 4 days (Days 0-3) after vaccination.

Population: The Total Vaccinated cohort included all vaccinated subjects.

Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events was actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre (mm)

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Any pain	27 Participants	13 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Grade 3 pain	0 Participants	0 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Any redness	1 Participants	1 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Redness > 30 mm	0 Participants	1 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Any swelling	4 Participants	2 Participants
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. Swelling > 30 mm	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 4 days (Days 0-3) after vaccination.

Population: The Total Vaccinated cohort included all vaccinated subjects.

Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = temperature \>39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Any drowsiness	2 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Grade 3 drowsiness	0 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Related drowsiness	2 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Fever >= 37.5°C	8 Participants	3 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Fever > 39.5°C	0 Participants	1 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Related fever	8 Participants	3 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Any irritability	2 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Grade 3 irritability	0 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Related irritability	2 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Any loss of appetite	1 Participants	1 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Grade 3 loss of appetite	0 Participants	0 Participants
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs. Related loss of appetite	1 Participants	1 Participants

SECONDARY outcome

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

Population: The Total Vaccinated cohort included all vaccinated subjects.

Unsolicited AEs = Any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Number of Subjects Reporting Unsolicited AEs.	31 Participants	18 Participants

SECONDARY outcome

Timeframe: During the entire study period, from the vaccination visit at Day 0 up to the end of the follow-up visit at Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group.

Population: The Total Vaccinated cohort included all vaccinated subjects.

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Outcome measures

Outcome measures
Measure	Synflorix/Infanrix Primed Group n=68 Participants Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 Participants Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Number of Subjects Reporting Serious Adverse Events (SAEs).	1 Participants	0 Participants

Adverse Events

Synflorix/Infanrix Primed Group

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Synflorix/Infanrix Unprimed Group

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Synflorix/Infanrix Primed Group n=68 participants at risk Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 participants at risk Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
General disorders Drowning	1.5% 1/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	0.00% 0/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.

Other adverse events

Other adverse events
Measure	Synflorix/Infanrix Primed Group n=68 participants at risk Subjects previously primed with the Synflorix™ vaccine in the primary study NCT00678301 received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.	Synflorix/Infanrix Unprimed Group n=36 participants at risk Unprimed subjects from the primary study NCT00678301, not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm.
Infections and infestations Respiratory tract infection	19.1% 13/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	19.4% 7/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
Infections and infestations Malaria	11.8% 8/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	27.8% 10/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
Eye disorders Conjunctivitis	4.4% 3/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	5.6% 2/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
Infections and infestations Furuncle	5.9% 4/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	2.8% 1/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
Infections and infestations Upper respiratory tract infection	4.4% 3/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	5.6% 2/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
Gastrointestinal disorders Enteritis	0.00% 0/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	5.6% 2/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
General disorders Fever	11.8% 8/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	8.3% 3/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
General disorders Pain	39.7% 27/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	36.1% 13/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.
General disorders Swelling	5.9% 4/68 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.	5.6% 2/36 • Solicited AEs: Within 4 days (Days 0-3) after vaccination. Unsolicited AEs: Within 31 days (Days 0-30) after vaccination. SAEs: From Day 0 up to Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. Because of an issue discovered with the informed consent obtained for one child after the original statistical analysis. The data of the child, who also had an SAE that was not considered to be related to the study medication by the investigator, have been removed from the results tables.

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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