Trial Outcomes & Findings for Booster Vaccination Study With a Pneumococcal Vaccine in Children Primed With the Same Vaccine (NCT NCT00911144)

NCT ID: NCT00911144

Last Updated: 2018-09-20

Results Overview

Grade 3 adverse events are severe symptoms that prevent normal, everyday activities.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 450 participants
• Primary outcome timeframe: Within 31 days (Day 0 - Day 30) after booster vaccination.
• Results posted on: 2018-09-20

Participant Flow

Two subjects enrolled in the protocol received commercial Prevenar and Hiberix vaccines instead of the clinical vaccines planned to be injected and are as such not included in the number of started subjects below.

Participant milestones

Measure	Synflorix Group Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Overall Study STARTED	335	113
Overall Study COMPLETED	319	108
Overall Study NOT COMPLETED	16	5

Reasons for withdrawal

Measure	Synflorix Group Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Overall Study Withdrawal by Subject	16	5

Baseline Characteristics

Booster Vaccination Study With a Pneumococcal Vaccine in Children Primed With the Same Vaccine

Baseline characteristics by cohort

Measure	Synflorix Group n=335 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Total n=448 Participants Total of all reporting groups
Age, Continuous	13.6 months STANDARD_DEVIATION 1.07 • n=5 Participants	13.7 months STANDARD_DEVIATION 1.00 • n=7 Participants	13.6 months STANDARD_DEVIATION 1.05 • n=5 Participants
Sex: Female, Male Female	168 Participants n=5 Participants	59 Participants n=7 Participants	227 Participants n=5 Participants
Sex: Female, Male Male	167 Participants n=5 Participants	54 Participants n=7 Participants	221 Participants n=5 Participants

PRIMARY outcome

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

Population: Analysis was performed on the Total vaccinated cohort on the subjects with available data.

Grade 3 adverse events are severe symptoms that prevent normal, everyday activities.

Outcome measures

Measure	Synflorix Group n=332 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Number of Subjects Reporting Grade 3 Adverse Events	42 Participants	13 Participants

SECONDARY outcome

Timeframe: Within 4 days (Days 0 to 3) after booster vaccination

Population: Analysis was performed on the Total vaccinated cohort on the subjects with available data.

Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, fever (equal to or above 37.5 degrees Celsius), irritability and loss of appetite.

Outcome measures

Measure	Synflorix Group n=332 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Number of Subjects Reporting Solicited Symptoms Pain	120 Participants	39 Participants
Number of Subjects Reporting Solicited Symptoms Redness	142 Participants	55 Participants
Number of Subjects Reporting Solicited Symptoms Swelling	97 Participants	35 Participants
Number of Subjects Reporting Solicited Symptoms Drowsiness	75 Participants	21 Participants
Number of Subjects Reporting Solicited Symptoms Fever	46 Participants	20 Participants
Number of Subjects Reporting Solicited Symptoms Irritability	141 Participants	42 Participants
Number of Subjects Reporting Solicited Symptoms Loss of appetite	71 Participants	29 Participants

SECONDARY outcome

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

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

Outcome measures

Measure	Synflorix Group n=335 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Number of Subjects Reporting Unsolicited Adverse Events	118 Participants	41 Participants

SECONDARY outcome

Timeframe: After booster vaccination up to study end (Month 0 to Month 1)

Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

Outcome measures

Measure	Synflorix Group n=335 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Number of Subjects Reporting Serious Adverse Events	8 Participants	4 Participants

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Concentrations of antibodies are measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations expressed as microgram per milliliter (ug/mL).

Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Outcome measures

Measure	Synflorix Group n=317 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=102 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-1	4.03 ug/mL Interval 3.66 to 4.43	0.06 ug/mL Interval 0.05 to 0.07
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-4	5.77 ug/mL Interval 5.25 to 6.34	12.19 ug/mL Interval 10.11 to 14.69
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-5	5.51 ug/mL Interval 5.08 to 5.98	0.19 ug/mL Interval 0.16 to 0.23
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-6B	2.78 ug/mL Interval 2.48 to 3.12	7.09 ug/mL Interval 5.82 to 8.63
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-7F	5.39 ug/mL Interval 4.97 to 5.85	0.06 ug/mL Interval 0.04 to 0.07
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-9V	4.99 ug/mL Interval 4.55 to 5.46	12.72 ug/mL Interval 10.86 to 14.88
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-14	7.73 ug/mL Interval 7.09 to 8.43	22.22 ug/mL Interval 18.96 to 26.03
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-18C	13.14 ug/mL Interval 11.9 to 14.52	14.53 ug/mL Interval 12.1 to 17.44
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-19F	16.89 ug/mL Interval 14.87 to 19.2	4.82 ug/mL Interval 3.97 to 5.85
Concentration of Antibodies Against Vaccine Pneumococcal Serotypes Anti-23F	3.75 ug/mL Interval 3.37 to 4.16	14.81 ug/mL Interval 11.61 to 18.89

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions.

Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Outcome measures

Measure	Synflorix Group n=151 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=47 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-1	363.7 titer Interval 275.3 to 480.5	4.7 titer Interval 3.9 to 5.6
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-4	1058.0 titer Interval 893.9 to 1252.3	3717.0 titer Interval 2759.3 to 5007.0
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-5	233.9 titer Interval 189.8 to 288.3	4.0 titer Interval 4.0 to 4.0
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-6B	546.5 titer Interval 415.9 to 718.0	3826.8 titer Interval 2518.0 to 5815.9
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-7F	5467.5 titer Interval 4698.1 to 6363.0	1038.2 titer Interval 609.9 to 1767.2
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-9V	1707.5 titer Interval 1497.6 to 1946.8	5204.0 titer Interval 3842.8 to 7047.4
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-14	1814.6 titer Interval 1577.4 to 2087.5	3958.4 titer Interval 2888.1 to 5425.4
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-18C	607.9 titer Interval 498.2 to 741.6	1723.3 titer Interval 1196.4 to 2482.3
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-19F	1284.5 titer Interval 1027.2 to 1606.3	277.3 titer Interval 171.6 to 448.2
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Opsono-23F	2702.9 titer Interval 2234.9 to 3268.9	29918.6 titer Interval 17115.7 to 52298.1

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Concentrations of antibodies are measured by 22F-inhibition ELISA and are presented as geometric mean concentrations expressed as microgram per milliliter.

Outcome measures

Measure	Synflorix Group n=317 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=102 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-6A	0.99 ug/mL Interval 0.84 to 1.17	2.51 ug/mL Interval 1.79 to 3.51
Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Anti-19A	1.54 ug/mL Interval 1.27 to 1.87	0.32 ug/mL Interval 0.24 to 0.43

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions.

Outcome measures

Measure	Synflorix Group n=146 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=44 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-6A	196.1 titer Interval 134.6 to 285.9	1415.7 titer Interval 891.2 to 2248.9
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A Opsono-19A	64.9 titer Interval 44.6 to 94.5	15.5 titer Interval 8.1 to 29.9

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per milliliter (EU/mL).

Outcome measures

Measure	Synflorix Group n=316 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=101 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Concentration of Antibodies Against Protein D (PD)	1288.9 EU/mL Interval 1175.6 to 1413.2	92.0 EU/mL Interval 78.3 to 108.1

SECONDARY outcome

Timeframe: One month after booster vaccination (Month 1)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data were available for antibodies against at least one study vaccine antigen after booster vaccination.

Concentrations of antibodies are presented as geometric mean concentrations expressed as microgram per milliliter.

Outcome measures

Measure	Synflorix Group n=163 Participants Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=54 Participants Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP)	152.970 ug/mL Interval 130.307 to 179.575	99.738 ug/mL Interval 72.964 to 136.335

Adverse Events

Synflorix Group

Serious events: 8 serious events

Other events: 243 other events

Deaths: 0 deaths

Prevenar Group

Serious events: 4 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Measure	Synflorix Group n=335 participants at risk Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 participants at risk Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Infections and infestations Pharyngitis	0.00% 0/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	1.8% 2/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Pharyngotonsillitis	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.88% 1/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Pneumonia	0.60% 2/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Bronchopneumonia	0.00% 0/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.88% 1/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Nervous system disorders Febrile convulsion	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Gastroenteritis rotavirus	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations H1N1 influenza	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Hand-foot-and-mouth disease	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Otitis media acute	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Pyrexia	0.00% 0/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.88% 1/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Skin and subcutaneous tissue disorders Urticaria	0.30% 1/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	0.00% 0/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.

Other adverse events

Measure	Synflorix Group n=335 participants at risk Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.	Prevenar Group n=113 participants at risk Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively.
Infections and infestations Upper respiratory tract infection	9.0% 30/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	10.6% 12/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
Infections and infestations Nasopharyngitis	5.7% 19/335 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	8.8% 10/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Pain at the injection site	36.1% 120/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	34.5% 39/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Redness at the injection site	42.8% 142/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	48.7% 55/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Swelling at the injection site	29.2% 97/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	31.0% 35/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Drowsiness	22.6% 75/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	18.6% 21/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Fever	13.9% 46/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	17.7% 20/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Irritability	42.5% 141/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	37.2% 42/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.
General disorders Loss of appetite	21.4% 71/332 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.	25.7% 29/113 • Serious AEs were assessed up to one month following booster vaccination (Month 1). The time frames for Other AEs reporting were 4 days and 31 days following booster vaccination for events collected by systematic and non-systematic methods, respectively. Subjects at risk for systematically assessed other (non-serious) adverse events has been set to the number of subjects that had returned their symptom sheet.

Additional Information

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