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Clinical Trial Results:
A phase II, randomized, controlled, partially-blind study to demonstrate immunogenicity and assess safety of GlaxoSmithKline (GSK) Biologicals’ pneumococcal vaccines (2830929A and 2830930A) administered as a 3-dose primary vaccination course during the first 6 months of life and as a booster dose at 12-15 months of age.

Summary
EudraCT number	2011-005743-27
Trial protocol	CZ ES DE PL
Global end of trial date	22 Jan 2014

Results information
Results version number	v3(current)
This version publication date	10 Feb 2019
First version publication date	27 May 2015
Other versions	v1 , v2
Version creation reason	New data added to full data set Immunogenicity data to be added regarding serotypes 6A and 19A

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

116485

ISRCTN number

US NCT number

NCT01616459

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l'Institut 89, Rixensart, Belgium, 1330

Public contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, +44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, +44 2089904466, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

26 Oct 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Jan 2014

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that 2830929A vaccine co-administered with DTPa-HBV-IPV/Hib as a three-dose primary vaccination course at approximately 2, 3, 4 months of age is non-inferior to Prevnar 13 or Synflorix in terms of percentage of subjects with antibody concentrations greater or equal to the seropositivity threshold and in terms of ELISA Geometric Mean Concentrations (GMCs). To demonstrate that 2830930A vaccine co-administered with DTPa-HBV-IPV/Hib at approximately 2, 3, 4 months of age is non-inferior to Prevnar 13 or Synflorix in terms of percentage of subjects with antibody concentrations greater or equal to the seropositivity threshold and in terms of ELISA GMCs.

Protection of trial subjects

All subjects were supervised for 30 min after vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Only eligible subjects that had no contraindications to any components of the vaccines were vaccinated. Subjects were followed-up for 30 days after each/last vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jul 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 150

Country: Number of subjects enrolled

Spain: 398

Country: Number of subjects enrolled

Czech Republic: 253

Country: Number of subjects enrolled

Germany: 152

Worldwide total number of subjects

953

EEA total number of subjects

953

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

953

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

953 subjects were enrolled in the study, among whom 951 received at least one dose of study vaccine, while 2 were allocated a subject number but did not receive any study vaccine dose.

Screening details

Study vaccines were administered as a 3-dose primary vaccination in healthy infants between 6-12 weeks (42-90 days) of age at the time of the first vaccination (Primary Phase), and then as an additional booster dose when subjects reached 12-15 months of age (Booster Phase).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

11Pn Group

Arm description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Arm type

Experimental

Investigational medicinal product name

Pneumococcal conjugate vaccine GSK2830929A

Investigational medicinal product code

Other name

11Pn

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

Other name

DTPA-HBV-IPV/Hib

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

12Pn Group

Arm description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Arm type

Experimental

Investigational medicinal product name

Pneumococcal conjugate vaccine GSK2830930A

Investigational medicinal product code

Other name

12Pn

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

Other name

DTPA-HBV-IPV/Hib

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Synflorix Group

Arm description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Arm type

Active comparator

Investigational medicinal product name

Synflorix™

Investigational medicinal product code

Other name

10Pn

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

Other name

DTPA-HBV-IPV/Hib

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar13 Group

Arm description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Arm type

Active comparator

Investigational medicinal product name

Prevnar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

Other name

DTPA-HBV-IPV/Hib

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1 ^[1]	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Started	240	240	230	241
Completed	236	223	220	233
Not completed	4	17	10	8
Consent withdrawn by subject	2	4	4	4
Adverse event, non-fatal	1	1	2	-
Consent withdrawal/not willing to participate not	-	1	1	-
Lost to follow-up	1	11	3	2
Protocol deviation	-	-	-	2

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Although 953 subjects were enrolled, only 951 subjects started the study and were vaccinated.

Baseline characteristics

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Reporting group title

11Pn Group

Reporting group description

Reporting group title

12Pn Group

Reporting group description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Reporting group title

Synflorix Group

Reporting group description

Reporting group title

Prevnar13 Group

Reporting group description

Reporting group values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group	Total
Number of subjects	240	240	230	241	951
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	8.6 ± 1.49	8.7 ± 1.61	8.7 ± 1.62	8.6 ± 1.54	-
Gender categorical
Units: Subjects
Female	113	120	113	121	467
Male	127	120	117	120	484

End points

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Reporting group title

11Pn Group

Reporting group description

Reporting group title

12Pn Group

Reporting group description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Reporting group title

Synflorix Group

Reporting group description

Reporting group title

Prevnar13 Group

Reporting group description

Primary: Antibody concentrations against pneumococcal serotypes during the Primary Phase of the study

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End point title

Antibody concentrations against pneumococcal serotypes during the Primary Phase of the study ^[1]

End point description

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. Primary outcome results correspond to antibody concentrations for all serotypes presented at the exception of those for the antibodies against the cross-reactive pneumococcal serotype 3 (ANTI-3). Analysis of concentrations of antibodies against the cross-reactive pneumococcal serotype 6C (ANTI-6C) was not performed due to unavailability of a specific qualified assay.

End point type

Primary

End point timeframe

At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	223	214	210	219
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1 (N=222,214,210,218)	1.54 (1.37 to 1.74)	1.59 (1.41 to 1.79)	1.37 (1.21 to 1.54)	2.18 (1.97 to 2.42)
ANTI-3 (N=221,214,209,218)	0.06 (0.05 to 0.06)	0.06 (0.05 to 0.07)	0.05 (0.05 to 0.06)	2.27 (2.06 to 2.49)
ANTI-4 (N=222,214,210,218)	1.78 (1.56 to 2.02)	1.99 (1.73 to 2.28)	1.68 (1.47 to 1.93)	2.83 (2.6 to 3.09)
ANTI-5 (N=222,214,209,218)	2.48 (2.24 to 2.74)	2.37 (2.13 to 2.64)	2.19 (1.97 to 2.44)	2.81 (2.52 to 3.13)
ANTI-6A (N=222,214,208,218)	0.14 (0.12 to 0.17)	1.12 (0.93 to 1.34)	0.12 (0.1 to 0.14)	2.05 (1.81 to 2.32)
ANTI-6B (N=222,214,210,218)	0.51 (0.42 to 0.61)	0.58 (0.48 to 0.69)	0.48 (0.4 to 0.58)	0.49 (0.42 to 0.58)
ANTI-7F (N=223,214,210,219)	2.3 (2.1 to 2.52)	2.44 (2.18 to 2.72)	2.2 (1.97 to 2.47)	3.16 (2.91 to 3.43)
ANTI-9V (N=222,214,210,218)	1.57 (1.4 to 1.76)	1.77 (1.58 to 1.97)	1.42 (1.27 to 1.59)	2.27 (2.05 to 2.51)
ANTI-14 (N=222,214,210,218)	4.19 (3.72 to 4.71)	4.45 (3.95 to 5)	4.21 (3.72 to 4.77)	4.2 (3.68 to 4.8)
ANTI-18C (N=222,214,210,219)	2.84 (2.45 to 3.28)	2.56 (2.21 to 2.96)	2.56 (2.19 to 2.98)	3.17 (2.87 to 3.51)
ANTI-19A (N=222,214,209,219)	1.63 (1.43 to 1.86)	1.18 (1.03 to 1.36)	0.18 (0.15 to 0.22)	2.67 (2.39 to 3)
ANTI-19F (N=223,214,210,218)	3.65 (3.2 to 4.16)	3.31 (2.91 to 3.76)	3.68 (3.15 to 4.3)	3.07 (2.83 to 3.34)
ANTI-23F (N=222,214,210,218)	0.62 (0.52 to 0.73)	0.69 (0.57 to 0.83)	0.72 (0.61 to 0.86)	1.59 (1.38 to 1.84)

No statistical analyses for this end point

Primary: Percentage (%) of subjects (Synflorix and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during the primary phase

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End point title

Percentage (%) of subjects (Synflorix and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during the primary phase ^[2]

End point description

N = number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the difference in terms of percentage of subjects between the 2 following groups: 11Pn group and Synflorix group.

End point values	11Pn Group	Synflorix Group
Number of subjects analysed	223	210
Units: percent
number (not applicable)
ANTI-1 (N=222,210)	99.5	98.6
ANTI-4 (N=222,210)	97.7	96.7
ANTI-5 (N=222,209)	100	99.5
ANTI-6B (N=222,210)	77.5	75.2
ANTI-7F (N=223,210)	99.6	99.5
ANTI-9V (N=222,210)	98.6	99
ANTI-14 (N=222,210)	99.5	100
ANTI-18C (N=222,210)	99.1	98.1
ANTI-19F (N=223,210)	100	97.6
ANTI-23F (N=222,210)	81.1	83.8

(Synflorix - 11Pn) % subjects with ANTI-1≥0.2μg/mL

Statistical analysis description

To demonstrate that 11Pn co-administered with Infanrix hexa™ vaccine 1 month post-dose 3 was non-inferior for at least 9 out of 11 serotypes to Prevnar13 vaccine (for 19A) or Synflorix™ vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of % of subjects with antibody concentrations ≥ 0.2 μg/mL. Criteria: UL of the 2-sided 95.9% CI of the difference between (Prevnar13 minus 11Pn) and (Synflorix minus 11Pn) groups <10% for at least 9 out of 11 vaccine pneumococcal serotypes.

Comparison groups

Synflorix Group v 11Pn Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference in percentage

Point estimate

-0.98

Confidence interval

level

95.9%

sides

2-sided

lower limit

-3.89

upper limit

1.36

Notes
[3] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix - 11Pn) % subjects with ANTI-4≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Difference in percentage

Point estimate

-1.08

Confidence interval

level

95.9%

sides

2-sided

lower limit

-4.94

upper limit

2.45

Notes
[4] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix - 11Pn) % subjects with ANTI-5≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Difference in percentage

Point estimate

-0.48

Confidence interval

level

95.9%

sides

2-sided

lower limit

-2.82

upper limit

1.38

Notes
[5] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-6B≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Difference in percentage

Point estimate

-2.24

Confidence interval

level

95.9%

sides

2-sided

lower limit

-10.65

upper limit

6.13

Notes
[6] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-7F≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Difference in percentage

Point estimate

-0.03

Confidence interval

level

95.9%

sides

2-sided

lower limit

-2.39

upper limit

2.21

Notes
[7] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-9V≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Difference in percentage

Point estimate

0.4

Confidence interval

level

95.9%

sides

2-sided

lower limit

-2.36

upper limit

3.22

Notes
[8] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-14≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Difference in percentage

Point estimate

0.45

Confidence interval

level

95.9%

sides

2-sided

lower limit

-1.51

upper limit

2.66

Notes
[9] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-18C≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Difference in percentage

Point estimate

-1

Confidence interval

level

95.9%

sides

2-sided

lower limit

-4.18

upper limit

1.7

Notes
[10] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-19F≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Difference in percentage

Point estimate

-2.38

Confidence interval

level

95.9%

sides

2-sided

lower limit

-5.64

upper limit

-0.52

Notes
[11] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

(Synflorix-11Pn) % subjects with ANTI-23F≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Difference in percentage

Point estimate

2.73

Confidence interval

level

95.9%

sides

2-sided

lower limit

-4.84

upper limit

10.25

Notes
[12] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 11Pn Groups) for pneumococcal serotypes during primary phase

Top of page

End point title

Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 11Pn Groups) for pneumococcal serotypes during primary phase ^[13]

End point description

Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = number of subjects with both pre- and post-vaccination results available Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the GMCs ratio between the 2 following groups: 11Pn group and Synflorix group.

End point values	11Pn Group	Synflorix Group
Number of subjects analysed	219	203
Units: µg/mL
number (not applicable)
ANTI-1 (N=218, 203)	1.51	1.36
ANTI-4 (N=218,203)	1.77	1.66
ANTI-5 (N=218,201)	2.46	2.16
ANTI-6B (N=218,200)	0.51	0.47
ANTI-7F (N=219,202)	2.3	2.17
ANTI-9V (N=218,200)	1.56	1.4
ANTI-14 (N=218,201)	4.22	4.06
ANTI-18C (N=218,201)	2.81	2.57
ANTI-19F (N=218,202)	3.7	3.68
ANTI-23F (N=218,199)	0.62	0.71

(Synflorix/11Pn) GMCs ratio for ANTI-1 serotype

Statistical analysis description

To demonstrate that 11Pn co-administered with Infanrix hexa™ vaccine 1 month post-dose 3 was non-inferior for at least 9 out of 11 vaccine serotypes to Prevnar13 vaccine (for 19A) or Synflorix™ vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of Enzyme-linked immunosorbent assay (ELISA) GMCs. Criteria: UL of the 2-sided 95.9% CI of the ELISA GMC ratios (Prevnar13/11Pn) and (Synflorix/11Pn) groups < a limit of 2-fold for at least 9 out of 11 vaccine pneumococcal serotypes.

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.9

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.75

upper limit

1.07

Notes
[14] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha = 2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-4 serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.94

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.77

upper limit

1.14

Notes
[15] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-6B serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.93

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.71

upper limit

1.23

Notes
[16] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-7F serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.94

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.81

upper limit

1.1

Notes
[17] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-9V serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.89

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.76

upper limit

1.06

Notes
[18] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-14 serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.96

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.81

upper limit

1.15

Notes
[19] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-18C serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.92

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.74

upper limit

1.14

Notes
[20] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-19F serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.81

upper limit

1.23

Notes
[21] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-23F serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.15

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.89

upper limit

1.48

Notes
[22] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/11Pn) GMCs ratio for ANTI-5 serotype

Statistical analysis description

Comparison groups

11Pn Group v Synflorix Group

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.88

Confidence interval

level

95.9%

sides

2-sided

lower limit

0.75

upper limit

1.03

Notes
[23] - -2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) around the ELISA GMCs ratio between groups -GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

Primary: Percentage (%) of subjects (Prevnar13 and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for ANTI-19A pneumococcal serotype during primary phase

Top of page

End point title

Percentage (%) of subjects (Prevnar13 and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for ANTI-19A pneumococcal serotype during primary phase ^[24]

End point description

N = number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 19A (ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the difference in terms of percentage of subjects between the 2 following groups: 11Pn group and Prevnar13 group.

End point values	11Pn Group	Prevnar13 Group
Number of subjects analysed	222	219
Units: percent
number (not applicable)
ANTI-19A (N=222,219)	98.6	99.5

(Prevnar13-11Pn) % subjects with ANTI-19A≥0.2μg/mL

Statistical analysis description

Comparison groups

11Pn Group v Prevnar13 Group

Number of subjects included in analysis

441

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

Difference in percentage

Point estimate

0.89

Confidence interval

level

95.9%

sides

2-sided

lower limit

-1.46

upper limit

3.66

Notes
[25] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha =2.05%) of the difference between groups in terms of percentage of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used within GSK Biologicals is method 6.

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 11Pn Groups) for ANTI-19A pneumococcal serotype during primary phase

Top of page

End point title

Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 11Pn Groups) for ANTI-19A pneumococcal serotype during primary phase ^[26]

End point description

Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = number of subjects with both pre- and post-vaccination results available Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 19A (ANTI -19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the GMCs ratio between the 2 following groups: 11Pn group and Prevnar13 group.

End point values	11Pn Group	Prevnar13 Group
Number of subjects analysed	217	206
Units: μg/mL
number (not applicable)
ANTI-19A (N=217,206)	1.61	2.75

(Prevnar13/11Pn) GMCs ratio for ANTI-19A serotype

Statistical analysis description

Comparison groups

11Pn Group v Prevnar13 Group

Number of subjects included in analysis

423

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.71

Confidence interval

level

95.9%

sides

2-sided

lower limit

1.44

upper limit

2.03

Notes
[27] - 2-sided 95.9% Confidence Interval (CI) adjusted 1-sided alpha = 2.05%) around the ELISA GMCs ratio between groups GMCs ratio and its CI were obtained using an ANCOVA model on the logarithm-transformed concentrations/titres,including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

Primary: Percentage (%) of subjects (Synflorix and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during primary phase

Top of page

End point title

Percentage (%) of subjects (Synflorix and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during primary phase ^[28]

End point description

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the difference in terms of percentage of subjects between the 2 following groups: 12Pn group and Synflorix group.

End point values	12Pn Group	Synflorix Group
Number of subjects analysed	214	210
Units: percent
number (not applicable)
ANTI-1 (N=214,210)	99.1	98.6
ANTI-4 (N=214,210)	96.7	96.7
ANTI-5 (N=214,209)	99.5	99.5
ANTI-6B (N=214,210)	79.9	75.2
ANTI-7F (N=214,210)	99.1	99.5
ANTI-9V (N=214,210)	99.1	99
ANTI-14 (N=214,210)	100	100
ANTI-18C (N=214,210)	98.6	98.1
ANTI-19F (N=214,210)	98.6	97.6
ANTI-23F (N=214,210)	81.3	83.8

(Synflorix-12Pn) % subjects with ANTI-1≥0.2μg/mL

Statistical analysis description

To demonstrate that 12Pn co-administered with Infanrix hexa™ vaccine 1 month post-dose 3 was non-inferior for at least 10 out of 12 serotypes to Prevnar13 vaccine (for 6A and 19A) or Synflorix™ vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of % of subjects with antibody concentrations ≥ 0.2 μg/mL. Criteria: UL of the 2-sided 95.8%CI of the difference between (Prevnar13 minus 12Pn) and (Synflorix minus 12Pn) groups <10% for at least 10 out of 12 vaccine pneumococcal serotypes.

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

Difference in percentage

Point estimate

-0.49

Confidence interval

level

95.8%

sides

2-sided

lower limit

-3.44

upper limit

2.22

Notes
[29] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-4≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

Difference in percentage

Point estimate

-0.06

Confidence interval

level

95.8%

sides

2-sided

lower limit

-4.03

upper limit

3.86

Notes
[30] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-5≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

Parameter type

Difference in percentage

Point estimate

-0.01

Confidence interval

level

95.8%

sides

2-sided

lower limit

-2.37

upper limit

2.3

Notes
[31] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-6B≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

Parameter type

Difference in percentage

Point estimate

-4.67

Confidence interval

level

95.8%

sides

2-sided

lower limit

-12.94

upper limit

3.6

Notes
[32] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-7F≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

Parameter type

Difference in percentage

Point estimate

0.46

Confidence interval

level

95.8%

sides

2-sided

lower limit

-1.93

upper limit

3.06

Notes
[33] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-9V≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

Method

Parameter type

Difference in percentage

Point estimate

-0.02

Confidence interval

level

95.8%

sides

2-sided

lower limit

-2.72

upper limit

2.64

Notes
[34] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-14≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

Method

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95.8%

sides

2-sided

lower limit

-1.94

upper limit

1.9

Notes
[35] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-18C≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

Method

Parameter type

Difference in percentage

Point estimate

-0.5

Confidence interval

level

95.8%

sides

2-sided

lower limit

-3.72

upper limit

2.52

Notes
[36] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-19F≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

Method

Parameter type

Difference in percentage

Point estimate

-0.98

Confidence interval

level

95.8%

sides

2-sided

lower limit

-4.38

upper limit

2.1

Notes
[37] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Synflorix-12Pn) % subjects with ANTI-23F≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

Method

Parameter type

Difference in percentage

Point estimate

2.5

Confidence interval

level

95.8%

sides

2-sided

lower limit

-5.07

upper limit

10.06

Notes
[38] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 12Pn Groups) for pneumococcal serotypes during primary phase

Top of page

End point title

Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 12Pn Groups) for pneumococcal serotypes during primary phase ^[39]

End point description

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the GMCs ratio between the 2 following groups: 12Pn group and Synflorix group.

End point values	12Pn Group	Synflorix Group
Number of subjects analysed	211	203
Units: µg/mL
number (not applicable)
ANTI-1 (N=207,203)	1.58	1.35
ANTI-4 (N=208,203)	1.94	1.66
ANTI-5 (N=208,201)	2.37	2.16
ANTI-6B (N=208,200)	0.56	0.47
ANTI-7F (N=211,202)	2.42	2.17
ANTI-9V (N=208,200)	1.78	1.4
ANTI-14 (N=209,201)	4.48	4.1
ANTI-18C (N=209,201)	2.55	2.57
ANTI-19F (N=211,202)	3.29	3.67
ANTI-23F (N=208,199)	0.68	0.71

(Synflorix/12Pn) GMCs ratio for ANTI-1 serotype

Statistical analysis description

To demonstrate that 12Pn co-administered with Infanrix hexa™ vaccine 1 month post-dose 3 was non-inferior for at least 10 out of 12 vaccine serotypes to Prevnar13 vaccine (for 6A & 19A) or Synflorix™ vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of Enzyme-linked immunosorbent assay (ELISA) GMCs. Criteria: UL of the 2-sided 95.8% CI of the ELISA GMC ratios (Prevnar13/12Pn) and (Synflorix/12Pn) groups < a limit of 2-fold for at least 10 out of 12 vaccine pneumococcal serotypes.

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.86

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.72

upper limit

1.02

Notes
[40] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-4 serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.86

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.7

upper limit

1.05

Notes
[41] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-5 serotype

Statistical analysis description

Comparison groups

Synflorix Group v 12Pn Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.91

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.78

upper limit

1.07

Notes
[42] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-6B serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.84

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.64

upper limit

1.11

Notes
[43] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-7F serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.9

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.76

upper limit

1.06

Notes
[44] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-9V serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.79

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.67

upper limit

0.93

Notes
[45] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-14 serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

0.91

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.77

upper limit

1.09

Notes
[46] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-18C serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.01

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.81

upper limit

1.26

Notes
[47] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration ofobjectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-19F serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.12

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.9

upper limit

1.38

Notes
[48] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Synflorix/12Pn) GMCs ratio for ANTI-23F serotype

Statistical analysis description

Comparison groups

12Pn Group v Synflorix Group

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.05

Confidence interval

level

95.8%

sides

2-sided

lower limit

0.81

upper limit

1.37

Notes
[49] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

Primary: Percentage (%) of subjects (Prevnar13 and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for anti-6A and anti-19A pneumococcal serotypes during primary phase

Top of page

End point title

Percentage (%) of subjects (Prevnar13 and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for anti-6A and anti-19A pneumococcal serotypes during primary phase ^[50]

End point description

N = number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI-6A and ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the difference in terms of percentage of subjects between the 2 following groups: 12Pn group and Prevnar13 group.

End point values	12Pn Group	Prevnar13 Group
Number of subjects analysed	214	219
Units: percent
number (not applicable)
ANTI-6A (N=214,218)	88.3	99.5
ANTI-19A (N=214,219)	95.8	99.5

(Prevnar13-12Pn) % subjects with ANTI-6A≥ 0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Prevnar13 Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

Method

Parameter type

Difference in percentage

Point estimate

11.22

Confidence interval

level

95.8%

sides

2-sided

lower limit

7.22

upper limit

16.49

Notes
[51] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

(Prevnar13-12Pn) % subjects with ANTI-19A≥0.2μg/mL

Statistical analysis description

Comparison groups

12Pn Group v Prevnar13 Group

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

Method

Parameter type

Difference in percentage

Point estimate

3.75

Confidence interval

level

95.8%

sides

2-sided

lower limit

1.03

upper limit

7.57

Notes
[52] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) of the difference between groups in terms of % of subjects. Confidence Interval (CI) for difference in proportion: Proc StatXact was used to derive the standardized asymptotic CI for the group difference in proportions [Newcombe, 1998]. The standardized asymptotic method used is method 6.

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 12Pn Groups) for anti-6A and anti-19A pneumococcal serotypes during primary phase

Top of page

End point title

Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 12Pn Groups) for anti-6A and anti-19A pneumococcal serotypes during primary phase ^[53]

End point description

Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = number of subjects with both pre- and post-vaccination results available Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A and 19A (ANTI -6A and ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).

End point type

Primary

End point timeframe

1 month post-dose 3 (primary phase)

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the analysis of the GMCs ratio between the 2 following groups: 12Pn group and Prevnar13 group.

End point values	12Pn Group	Prevnar13 Group
Number of subjects analysed	210	214
Units: µg/mL
number (not applicable)
ANTI-6A (N=210,214)	1.09	2.07
ANTI-19A (N=208,206)	1.19	2.76

(Prevnar13/12Pn) GMCs ratio for ANTI-6A serotype

Statistical analysis description

Comparison groups

12Pn Group v Prevnar13 Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

1.9

Confidence interval

level

95.8%

sides

2-sided

lower limit

1.51

upper limit

2.39

Notes
[54] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

(Prevnar13/12Pn) GMCs ratio for ANTI-19A serotype

Statistical analysis description

Comparison groups

12Pn Group v Prevnar13 Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

Method

Parameter type

Adjusted GMCs ratio

Point estimate

2.32

Confidence interval

level

95.8%

sides

2-sided

lower limit

1.94

upper limit

2.77

Notes
[55] - Objectives for 12-valent formulation were to be assessed sequentially after demonstration of objectives for 11-valent formulation. 2-sided 95.8% Confidence Interval (CI) adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups. GMCs ratio and CI were obtained using ANCOVA model on the logarithm-transformed concentrations/titres, including the vaccine group as fixed effect and the pre-vaccination concentration as regressor.

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Primary Phase of the study

Top of page

End point title

Concentrations of antibodies against protein D (Anti-PD) during the Primary Phase of the study

End point description

Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (≥) 100 EL.U/mL.

End point type

Secondary

End point timeframe

At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	112	106	103	106
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD	1430.1 (1194.2 to 1712.7)	1194.2 (1017.7 to 1401.3)	1344.8 (1116.4 to 1619.9)	64.4 (57.7 to 71.9)

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Primary Phase of the study

Top of page

End point title

Number of subjects with any and Grade 3 solicited local symptoms during the Primary Phase of the study

End point description

Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm).

End point type

Secondary

End point timeframe

Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	240	236	228	238
Units: Subjects
Any Pain, post D1 (N=240;236;228;238)	104	105	94	85
Grade 3 Pain, post D1 (N=240;236;228;238)	16	5	12	6
Any Redness, post D1 (N=240;236;228;238)	82	90	72	75
Grade 3 Redness, post D1 (N=240;236;228;238)	0	0	1	0
Any Swelling, post D1 (N=240;236;228;238)	51	57	46	47
Grade 3 Swelling, post D1 (N=240;236;228;238)	1	4	7	1
Any Pain, post D2 (N=239;232;227;234)	89	100	88	90
Grade 3 Pain, post D2 (N=239;232;227;234)	12	12	10	6
Any Redness, post D2 (N=239;232;227;234)	86	95	78	79
Grade 3 Redness, post D2 (N=239;232;227;234)	2	1	1	1
Any Swelling, post D2 (N=239;232;227;234)	61	72	54	49
Grade 3 Swelling, post D2 (N=239;232;227;234)	2	3	5	2
Any Pain, post D3 (N=238;229;226;234)	76	75	76	75
Grade 3 Pain, post D3 (N=238;229;226;234)	4	4	6	3
Any Redness, post D3 (N=238;229;226;234)	93	85	91	85
Grade 3 Redness, post D3 (N=238;229;226;234)	3	2	2	1
Any Swelling, post D3 (N=238;229;226;234)	72	76	58	61
Grade 3 Swelling, post D3 (N=238;229;226;234)	2	5	2	3

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Booster Phase of the study

Top of page

End point title

Number of subjects with any and Grade 3 solicited local symptoms during the Booster Phase of the study

End point description

End point type

Secondary

End point timeframe

Within the 4-day (Days 0-3) period after booster vaccination

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	235	224	219	231
Units: Subjects
Any Pain	112	123	119	110
Grade 3 Pain	13	16	18	8
Any Redness	109	117	108	107
Grade 3 Redness	5	10	7	5
Any Swelling	84	88	89	85
Grade 3 Swelling	8	7	5	7

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Primary Phase of the study

Top of page

End point title

Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Primary Phase of the study

End point description

Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [≥] 38.0 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C.

End point type

Secondary

End point timeframe

Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	240	236	227	238
Units: Subjects
Any Drowsiness, post D1 (N=240;236;227;238)	148	144	129	129
Grade 3 Drowsiness, post D1 (N=240;236;227;238)	7	6	10	10
Related Drowsiness, post D1 (N=240;236;227;238)	124	104	95	103
Any Irr./Fuss., post D1 (N=240;236;227;238)	151	156	134	138
Grade 3 Irr./Fuss., post D1 (N=240;236;227;238)	16	15	17	10
Related Irr./Fuss., post D1 (N=240;236;227;238)	119	122	98	103
Any Loss Appet., post D1 (N=240;236;227;238)	85	89	81	73
Grade 3 Loss Appet., post D1 (N=240;236;227;238)	2	2	3	2
Related Loss Appet., post D1 (N=240;236;227;238)	59	65	56	57
Any Fever, post D1 (N=240;236;227;238)	108	104	107	87
Grade 3 Fever, post D1 (N=240;236;227;238)	0	0	0	0
Related Fever, post D1 (N=240;236;227;238)	94	91	92	76
Any Drowsiness, post D2 (N=239;232;227;234)	125	115	105	111
Grade 3 Drowsiness, post D2 (N=239;232;227;234)	6	7	6	8
Related Drowsiness, post D2 (N=239;232;227;234)	96	89	81	97
Any Irr./Fuss., post D2 (N=239;232;227;234)	151	151	141	128
Grade 3 Irr./Fuss., post D2 (N=239;232;227;234)	18	12	17	10
Related Irr./Fuss., post D2 (N=239;232;227;234)	123	113	114	106
Any Loss Appet., post D2 (N=239;232;227;234)	69	78	71	72
Grade 3 Loss Appet., post D2 (N=239;232;227;234)	2	3	1	3
Related Loss Appet., post D2 (N=239;232;227;234)	52	58	48	56
Any Fever, post D2 (N=239;232;227;234)	97	84	90	90
Grade 3 Fever, post D2 (N=239;232;227;234)	0	0	0	0
Related Fever, post D2 (N=239;232;227;234)	87	75	82	82
Any Drowsiness, post D3 (N=238;229;227;234)	99	92	88	87
Grade 3 Drowsiness, post D3 (N=238;229;227;234)	4	2	3	5
Related Drowsiness, post D3 (N=238;229;227;234)	80	67	70	71
Any Irr./Fuss., post D3 (N=238;229;227;234)	117	123	118	112
Grade 3 Irr./Fuss., post D3 (N=238;229;227;234)	6	7	8	7
Related Irr./Fuss., post D3 (N=238;229;227;234)	95	92	96	87
Any Loss Appet., post D3 (N=238;229;227;234)	63	62	67	54
Grade 3 Loss Appet., post D3 (N=238;229;227;234)	0	3	3	5
Related Loss Appet., post D3 (N=238;229;227;234)	49	42	54	41
Any Fever, post D3 (N=238;229;227;234)	51	53	61	58
Grade 3 Fever, post D3 (N=238;229;227;234)	0	0	0	0
Related Fever, post D3 (N=238;229;227;234)	50	51	56	49

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Booster Phase of the study

Top of page

End point title

Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Booster Phase of the study

End point description

End point type

Secondary

End point timeframe

Within the 4-day (Days 0-3) period after booster vaccination

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	235	224	219	231
Units: Subjects
Any Drowsiness	109	100	84	96
Grade 3 Drowsiness	9	6	4	2
Related Drowsiness	93	79	68	81
Any Irr./Fuss.	140	136	137	129
Grade 3 Irr./Fuss.	14	14	12	9
Related Irr./Fuss.	107	117	109	107
Any Loss Appet.	80	85	83	61
Grade 3 Loss Appet.	6	3	9	7
Related Loss Appet.	66	64	65	45
Any Fever	80	72	68	75
Grade 3 Fever	2	0	1	0
Related Fever	72	66	60	67

No statistical analyses for this end point

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Primary Phase of the study

Top of page

End point title

Number of subjects with any unsolicited adverse events (AEs) during the Primary Phase of the study

End point description

An unsolicited AE was defined as 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

End point type

Secondary

End point timeframe

Within the 31-day (Days 0-30) period post primary vaccination, across doses

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	240	240	230	241
Units: Subjects
Any AE(s)	110	108	123	124

No statistical analyses for this end point

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Booster Phase of the study

Top of page

End point title

Number of subjects with any unsolicited adverse events (AEs) during the Booster Phase of the study

End point description

End point type

Secondary

End point timeframe

Within the 31-day (Days 0-30) period post booster vaccination

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	237	226	222	234
Units: Subjects
Any AE(s)	69	68	74	53

No statistical analyses for this end point

Secondary: Number of subjects with any serious adverse events (SAEs) during the Primary Phase of the study

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End point title

Number of subjects with any serious adverse events (SAEs) during the Primary Phase of the study

End point description

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.

End point type

Secondary

End point timeframe

From Month 0 to Month 3

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	240	240	230	241
Units: Subjects
Any SAE(s)	12	11	17	12

No statistical analyses for this end point

Secondary: Number of subjects with any serious adverse events (SAEs) during the entire duration of the study

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End point title

Number of subjects with any serious adverse events (SAEs) during the entire duration of the study

End point description

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.

End point type

Secondary

End point timeframe

From Day 0 to Month 11

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	240	240	230	241
Units: Subjects
Any SAE(s)	29	26	38	24

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes during the Booster Phase of the study

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End point title

Antibody concentrations against pneumococcal serotypes during the Booster Phase of the study

End point description

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. Analysis of concentrations of antibodies against the cross-reactive pneumococcal serotype 6C (ANTI-6C) was not performed due to unavailability of a specific qualified assay.

End point type

Secondary

End point timeframe

At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	216	206	203	210
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1 (M10) (N=216,206,202,210)	0.26 (0.24 to 0.3)	0.26 (0.24 to 0.3)	0.26 (0.23 to 0.29)	0.44 (0.4 to 0.48)
ANTI-1 (M11) (N=214,203,201,209)	2.49 (2.21 to 2.82)	2.18 (1.94 to 2.46)	2.25 (2.01 to 2.53)	3.84 (3.5 to 4.22)
ANTI-3 (M10) (N=214,204,199,208)	0.06 (0.05 to 0.07)	0.06 (0.05 to 0.06)	0.06 (0.05 to 0.07)	0.25 (0.22 to 0.29)
ANTI-3 (M11) (N=210,202,197,209)	0.07 (0.06 to 0.08)	0.07 (0.06 to 0.08)	0.07 (0.06 to 0.09)	1.68 (1.53 to 1.85)
ANTI-4 (M10) (N=213,203,203,210)	0.49 (0.44 to 0.54)	0.48 (0.43 to 0.54)	0.5 (0.45 to 0.56)	0.41 (0.37 to 0.46)
ANTI-4 (M11) (N=214,203,202,209)	3.89 (3.49 to 4.34)	4.18 (3.77 to 4.63)	4.06 (3.7 to 4.45)	3.86 (3.43 to 4.35)
ANTI-5 (M10) (N=213,202,199,208)	0.51 (0.46 to 0.57)	0.51 (0.45 to 0.57)	0.48 (0.43 to 0.53)	0.77 (0.69 to 0.85)
ANTI-5 (M11) (N=215,203,202,209)	3.23 (2.88 to 3.64)	3.31 (2.98 to 3.68)	3.05 (2.75 to 3.38)	6.84 (6.12 to 7.66)
ANTI-6B (M10) (N=213,202,199,209)	0.57 (0.49 to 0.65)	0.64 (0.56 to 0.74)	0.59 (0.51 to 0.69)	0.22 (0.19 to 0.25)
ANTI-6B (M11) (N=214,205,203,209)	2.66 (2.34 to 3.03)	4.09 (3.6 to 4.66)	2.53 (2.24 to 2.86)	3.8 (3.34 to 4.33)
ANTI-7F (M10) (N=213,203,200,207)	1.04 (0.94 to 1.16)	0.99 (0.89 to 1.1)	0.94 (0.84 to 1.05)	1.21 (1.11 to 1.32)
ANTI-7F (M11) (N=214,203,201,209)	4.88 (4.4 to 5.4)	4.57 (4.14 to 5.04)	4.31 (3.91 to 4.75)	6.34 (5.8 to 6.95)
ANTI-9V (M10) (N=213,202,198,207)	0.76 (0.68 to 0.85)	0.77 (0.69 to 0.87)	0.7 (0.63 to 0.77)	0.53 (0.48 to 0.58)
ANTI-9V (M11) (N=214,203,202,209)	4.14 (3.7 to 4.62)	4.36 (3.93 to 4.84)	3.68 (3.32 to 4.09)	5.83 (5.26 to 6.46)
ANTI-14 (M10) (N=214,204,201,209)	1.3 (1.11 to 1.53)	1.45 (1.28 to 1.64)	1.12 (0.97 to 1.3)	1.66 (1.44 to 1.93)
ANTI-14 (M11) (N=213,203,201,209)	6.17 (5.45 to 6.98)	6.52 (5.8 to 7.33)	5.75 (5.07 to 6.51)	10.05 (8.97 to 11.25)
ANTI-18C (M10) (N=212,200,195,207)	0.76 (0.67 to 0.86)	0.68 (0.6 to 0.77)	0.74 (0.65 to 0.84)	0.59 (0.54 to 0.65)
ANTI-18C (M11) (N=213,203,201,209)	7.65 (6.79 to 8.61)	7.2 (6.39 to 8.11)	8 (7.06 to 9.06)	6.01 (5.45 to 6.63)
ANTI-19A (M10) (N=212,199,197,208)	0.46 (0.39 to 0.54)	0.36 (0.31 to 0.42)	0.18 (0.15 to 0.21)	0.42 (0.35 to 0.49)
ANTI-19A (M11) (N=214,203,201,209)	5.35 (4.67 to 6.13)	4.46 (3.83 to 5.2)	1.11 (0.91 to 1.35)	7.06 (6.25 to 7.98)
ANTI-19F (M10) (N=212,199,196,207)	1.11 (0.97 to 1.28)	1.11 (0.96 to 1.29)	1.1 (0.95 to 1.29)	0.5 (0.44 to 0.57)
ANTI-19F (M11) (N=213,203,203,209)	8.67 (7.72 to 9.73)	8.5 (7.55 to 9.59)	8.22 (7.4 to 9.13)	6.4 (5.77 to 7.11)
ANTI-23F (M10) (N=214,205,198,208)	0.51 (0.44 to 0.58)	0.54 (0.47 to 0.62)	0.49 (0.43 to 0.56)	0.34 (0.29 to 0.39)
ANTI-23F (M11) (N=214,203,201,209)	3.09 (2.73 to 3.49)	3.31 (2.93 to 3.73)	2.98 (2.65 to 3.35)	6.49 (5.69 to 7.39)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Primary Phase of the study

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End point title

Titers for opsonophagocytic activity against pneumococcal serotypes during the Primary Phase of the study

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA -1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. Testing for opsonophagocytic activity against the cross reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay.

End point type

Secondary

End point timeframe

At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	105	105	99	105
Units: Titers
geometric mean (confidence interval 95%)
OPA-1 (N=105,105,98,105)	13.2 (9.6 to 18.2)	15.6 (11.4 to 21.1)	13.6 (9.9 to 18.6)	26.4 (19.3 to 36)
OPA-3 (N=101,100,94,100)	4.8 (4.2 to 5.5)	5.2 (4.4 to 6)	5 (4.3 to 5.7)	97.2 (81.6 to 116)
OPA-4 (N=103,105,99,104)	527.3 (401.5 to 692.4)	609 (492.8 to 752.5)	616.7 (503.2 to 756)	540.1 (444.7 to 656.1)
OPA-5 (N=102,104,98,105)	43 (32.6 to 56.9)	46.7 (36.8 to 59.3)	40.5 (30.4 to 54)	57.2 (44.3 to 74)
OPA-6A (N=100,103,94,103)	37.4 (22.9 to 60.9)	1292.6 (940.3 to 1777)	36.5 (22.6 to 59)	2832 (2212.8 to 3624.4)
OPA-6B (N=101,104,96,103)	478.3 (345.2 to 662.7)	603.2 (436.9 to 832.8)	622.6 (444.2 to 872.7)	742.3 (533.9 to 1031.8)
OPA-7F (N=104,103,98,104)	3515 (2787.1 to 4433)	4472.3 (3463.6 to 5774.9)	3424.1 (2631.9 to 4454.8)	9737.9 (7540.5 to 12575.8)
OPA-9V (N=105,105,98,104)	1212.9 (953.6 to 1542.6)	1629 (1293 to 2052.4)	1469.9 (1178.3 to 1833.6)	1614.5 (1283.9 to 2030.2)
OPA-14 (N=105,104,97,103)	1000.8 (743.1 to 1347.9)	1699.1 (1313.8 to 2197.3)	1417.4 (1059.6 to 1896)	2034.4 (1513.4 to 2734.8)
OPA-18C (N=105,102,98,102)	100.9 (67.7 to 150.4)	131.5 (86.9 to 198.8)	72 (47 to 110.4)	145.7 (102.6 to 206.8)
OPA-19F (N=102,102,96,103)	144.2 (101.8 to 204.3)	201.4 (147.2 to 275.4)	210.4 (143.6 to 308.2)	66 (49.8 to 87.5)
OPA-23F (N=104,104,98,104)	989.6 (652.9 to 1499.8)	1377.9 (951.5 to 1995.3)	1097.3 (742.1 to 1622.4)	5136.4 (3829.2 to 6889.8)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Booster Phase of the study

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End point title

Titers for opsonophagocytic activity against pneumococcal serotypes during the Booster Phase of the study

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA -1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. Testing for opsonophagocytic activity against the cross-reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay.

End point type

Secondary

End point timeframe

At study Month 11 , e.g.: at one month post booster vaccination with pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	99	97	96	101
Units: Titers
geometric mean (confidence interval 95%)
OPA-1 (N=99,97,96,101)	192.4 (129 to 287.1)	192.4 (133.3 to 277.5)	216.8 (148.3 to 316.9)	207.6 (145.8 to 295.6)
OPA-3 (N=93,89,85,96)	9.7 (7.5 to 12.7)	10.5 (8 to 13.7)	10.9 (7.6 to 15.5)	317.2 (275.4 to 365.4)
OPA-4 (N=96,96,95,100)	1455.3 (1208.9 to 1751.9)	1650.5 (1360.9 to 2001.9)	1550.5 (1230.2 to 1954.1)	1972.2 (1586.3 to 2451.9)
OPA-5 (N=99,96,96,100)	134.5 (100.3 to 180.4)	133.3 (105.2 to 168.8)	133.4 (100.5 to 177.1)	269.9 (216.2 to 337)
OPA-6A (N=95,93,92,98)	116.8 (67.9 to 201)	3436.7 (2716 to 4348.5)	146.4 (87.6 to 244.6)	5200.7 (4134.9 to 6541.3)
OPA-6B (N=98,96,95,100)	681.4 (520.3 to 892.5)	1246.4 (963.1 to 1613)	694.6 (546.5 to 882.6)	1727.9 (1406.2 to 2123.4)
OPA-7F (N=96,96,96,97)	8362.9 (6977.1 to 10023.9)	7516.4 (6223 to 9078.7)	7880.8 (6408.6 to 9691.3)	16592.6 (13909.7 to 19792.9)
OPA-9V (N=99,97,93,98)	3406.9 (2758.2 to 4208.1)	3616.1 (2838.1 to 4607.5)	3260.6 (2620.1 to 4057.6)	8470.4 (6692.4 to 10720.8)
OPA-14 (N=99,96,94,100)	2038.4 (1594.3 to 2606.2)	2519.9 (1960.2 to 3239.6)	2285.1 (1845.9 to 2828.9)	2772.6 (2218.6 to 3464.9)
OPA-18C (N=97,95,93,97)	914.8 (621.8 to 1345.9)	781.2 (536.3 to 1137.8)	912 (605.4 to 1374.1)	610.7 (421.3 to 885.1)
OPA-19F (N=95,96,96,98)	523.9 (382.9 to 716.8)	565.3 (406.4 to 786.6)	759.6 (554.3 to 1040.8)	438 (312.7 to 613.7)
OPA-23F (N=97,96,95,97)	2562.9 (2016.3 to 3257.6)	2923.6 (2248.9 to 3800.9)	2600 (1896.8 to 3563.9)	24350.4 (18303.2 to 32395.5)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Booster Phase of the study

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End point title

Concentrations of antibodies against protein D (Anti-PD) during the Booster Phase of the study

End point description

End point type

Secondary

End point timeframe

At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	108	102	101	106
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD (M10) (N=108,102,101,106)	445.87 (364.98 to 544.68)	447.55 (363.39 to 551.22)	459.99 (376.24 to 562.38)	70.87 (61.76 to 81.33)
Anti-PD (M11) (N=108,100,101,104)	1866.01 (1535.69 to 2267.38)	1835.49 (1511.45 to 2229.01)	2128.41 (1777.07 to 2549.21)	77.75 (67.1 to 90.09)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotype 6A during the Booster Phase of the study

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End point title

Antibody concentrations against pneumococcal serotype 6A during the Booster Phase of the study

End point description

Antibodies assessed for this outcome measure was that against the cross-reactive pneumococcal serotype 6A (ANTI-6A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (μg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 μg/mL.

End point type

Secondary

End point timeframe

At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	212	203	200	209
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-6A(M10)(N=211;196;194;205)	0.23 (0.19 to 0.27)	0.89 (0.78 to 1.01)	0.22 (0.18 to 0.26)	0.64 (0.56 to 0.73)
ANTI-6A(M11)(N=212;203;200;209)	1.07 (0.90 to 1.27)	7.94 (6.99 to 9.02)	0.91 (0.76 to 1.09)	9.31 (8.41 to 10.30)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Primary Phase

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End point title

Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Primary Phase

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) serotype-specific Lower Limit of Quantification (143).

End point type

Secondary

End point timeframe

At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	87	88	76	92
Units: Titers
geometric mean (confidence interval 95%)
OPA-19A	1813.0 (1524.4 to 2156.1)	1523.9 (1215.3 to 1910.9)	759.6 (559.2 to 1032.0)	2056.6 (1748.9 to 2418.4)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Booster Phase

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End point title

Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Booster Phase

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) serotype-specific Lower Limit of Quantification (143).

End point type

Secondary

End point timeframe

At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine

End point values	11Pn Group	12Pn Group	Synflorix Group	Prevnar13 Group
Number of subjects analysed	74	67	69	75
Units: Titers
geometric mean (confidence interval 95%)
OPA-19A	4866.4 (4184.6 to 5659.4)	3896.4 (3263.2 to 4652.4)	2191.0 (1720.0 to 2791.0)	5720.1 (4883.9 to 6699.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms: during the 4 days post-primary and post-booster vaccination. Unsolicited AEs: during 31 days post-primary and post-booster vaccination. SAEs: during the whole study period (from Day 0 to Month 11).

Adverse event reporting additional description

Analysis of AEs & SAEs performed on subjects who received at least one primary dose or at least the booster vaccination. Analysis of solicited symptoms performed on the same subjects and for whom results were available. Occurrences (all and “related to the treatment”) not calculated during the analysis are filled in with “subjects affected" info.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

12Pn Group

Reporting group description

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The first 3 doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Reporting group title

Synflorix Group

Reporting group description

Reporting group title

Prevnar13 Group

Reporting group description

Reporting group title

11Pn Group

Reporting group description

Serious adverse events	12Pn Group	Synflorix Group	Prevnar13 Group	11Pn Group
Total subjects affected by serious adverse events
subjects affected / exposed	26 / 240 (10.83%)	38 / 230 (16.52%)	24 / 241 (9.96%)	29 / 240 (12.08%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Retinoblastoma
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Concussion
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	1 / 230 (0.43%)	1 / 241 (0.41%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	1 / 230 (0.43%)	1 / 241 (0.41%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Exposure to toxic agent
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thermal burn
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Dacryostenosis congenital
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hypotonic-hyporesponsive episode
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myoclonus
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	2 / 230 (0.87%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Burning sensation
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotonia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	4 / 240 (1.67%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	2 / 4	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Milk allergy
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	2 / 240 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiectasis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis allergic
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ingrowing nail
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Conjunctivitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial pyelonephritis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Breast abscess
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	2 / 230 (0.87%)	3 / 241 (1.24%)	5 / 240 (2.08%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	7 / 230 (3.04%)	4 / 241 (1.66%)	5 / 240 (2.08%)
occurrences causally related to treatment / all	0 / 1	0 / 7	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis viral
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	2 / 240 (0.83%)	1 / 230 (0.43%)	2 / 241 (0.83%)	2 / 240 (0.83%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pertussis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	2 / 240 (0.83%)	3 / 230 (1.30%)	1 / 241 (0.41%)	3 / 240 (1.25%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	2 / 240 (0.83%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	4 / 230 (1.74%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	5 / 230 (2.17%)	1 / 241 (0.41%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tracheitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	3 / 230 (1.30%)	2 / 241 (0.83%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	2 / 230 (0.87%)	1 / 241 (0.41%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Impetigo
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	2 / 230 (0.87%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	2 / 230 (0.87%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adenoiditis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia pyelonephritis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis adenovirus
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral discitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media acute
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paronychia
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyomyositis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	0 / 230 (0.00%)	0 / 241 (0.00%)	1 / 240 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral tonsillitis
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	1 / 240 (0.42%)	0 / 230 (0.00%)	0 / 241 (0.00%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
Additional description: SAE reported between Day 0 and Month 11
subjects affected / exposed	0 / 240 (0.00%)	1 / 230 (0.43%)	1 / 241 (0.41%)	0 / 240 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	12Pn Group	Synflorix Group	Prevnar13 Group	11Pn Group
Total subjects affected by non serious adverse events
subjects affected / exposed	229 / 240 (95.42%)	221 / 230 (96.09%)	235 / 241 (97.51%)	234 / 240 (97.50%)
General disorders and administration site conditions
Pain (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[1]	141 / 236 (59.75%)	134 / 228 (58.77%)	126 / 238 (52.94%)	140 / 240 (58.33%)
occurrences all number	141	134	126	140
Redness (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[2]	144 / 236 (61.02%)	130 / 228 (57.02%)	134 / 238 (56.30%)	132 / 240 (55.00%)
occurrences all number	144	130	134	132
Swelling (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[3]	117 / 236 (49.58%)	91 / 228 (39.91%)	93 / 238 (39.08%)	108 / 240 (45.00%)
occurrences all number	117	91	93	108
Drowsiness (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[4]	178 / 236 (75.42%)	162 / 228 (71.05%)	168 / 238 (70.59%)	185 / 240 (77.08%)
occurrences all number	178	162	168	185
Irritability/Fussiness (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[5]	203 / 236 (86.02%)	185 / 228 (81.14%)	186 / 238 (78.15%)	202 / 240 (84.17%)
occurrences all number	203	185	186	202
Loss of appetite (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[6]	132 / 236 (55.93%)	125 / 228 (54.82%)	125 / 238 (52.52%)	124 / 240 (51.67%)
occurrences all number	132	125	125	124
Fever (rectal temperature ≥ 38°C) (primary phase)
alternative assessment type: Systematic
subjects affected / exposed ^[7]	144 / 236 (61.02%)	148 / 228 (64.91%)	143 / 238 (60.08%)	153 / 240 (63.75%)
occurrences all number	144	148	143	153
Pain (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[8]	123 / 224 (54.91%)	119 / 219 (54.34%)	110 / 231 (47.62%)	112 / 235 (47.66%)
occurrences all number	123	119	110	112
Redness (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[9]	117 / 224 (52.23%)	108 / 219 (49.32%)	107 / 231 (46.32%)	109 / 235 (46.38%)
occurrences all number	117	108	107	109
Swelling (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[10]	88 / 224 (39.29%)	89 / 219 (40.64%)	85 / 231 (36.80%)	84 / 235 (35.74%)
occurrences all number	88	89	85	84
Drowsiness (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[11]	100 / 224 (44.64%)	84 / 219 (38.36%)	96 / 231 (41.56%)	109 / 235 (46.38%)
occurrences all number	100	84	96	109
Irritability/Fusiness (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[12]	136 / 224 (60.71%)	137 / 219 (62.56%)	129 / 231 (55.84%)	140 / 235 (59.57%)
occurrences all number	136	137	129	140
Loss of appetite (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[13]	85 / 224 (37.95%)	83 / 219 (37.90%)	61 / 231 (26.41%)	80 / 235 (34.04%)
occurrences all number	85	83	61	80
Fever (rectal temperature ≥ 38°C) (booster phase)
Additional description: Symptom reported during the 4-day post-booster vaccination period
alternative assessment type: Systematic
subjects affected / exposed ^[14]	72 / 224 (32.14%)	68 / 219 (31.05%)	75 / 231 (32.47%)	80 / 235 (34.04%)
occurrences all number	72	68	75	80
Infections and infestations
Upper respiratory tract infection (primary phase)
subjects affected / exposed	39 / 240 (16.25%)	49 / 230 (21.30%)	28 / 241 (11.62%)	38 / 240 (15.83%)
occurrences all number	39	49	28	38
Rhinitis
subjects affected / exposed	15 / 240 (6.25%)	12 / 230 (5.22%)	16 / 241 (6.64%)	18 / 240 (7.50%)
occurrences all number	15	12	16	18
Bronchiolitis
subjects affected / exposed	10 / 240 (4.17%)	13 / 230 (5.65%)	11 / 241 (4.56%)	12 / 240 (5.00%)
occurrences all number	10	13	11	12
Bronchitis
subjects affected / exposed	7 / 240 (2.92%)	18 / 230 (7.83%)	16 / 241 (6.64%)	10 / 240 (4.17%)
occurrences all number	7	18	16	10
Nasopharyngitis
subjects affected / exposed	14 / 240 (5.83%)	8 / 230 (3.48%)	11 / 241 (4.56%)	10 / 240 (4.17%)
occurrences all number	14	8	11	10
Upper respiratory tract infection (booster phase)
Additional description: Unsolicited AE reported during the 31-day post-booster vaccination period
subjects affected / exposed ^[15]	16 / 226 (7.08%)	20 / 222 (9.01%)	13 / 234 (5.56%)	11 / 237 (4.64%)
occurrences all number	16	20	13	11

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results are presented only for subjects for whom results were available.

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Were there any global substantial amendments to the protocol? Yes

13 Feb 2013

Amendment 2 The protocol has been amended to include the opsonophagocytic activity (OPA) testing for pneumococcal serotypes 1, 3, 4, 5, 6B, 6C, 7F, 9V, 14, 18C, 19F and 23F, in addition to the previously planned OPA testing for serotypes 6A and 19A. This testing was added to gather further evidence, early in the clinical development, of any potential impact of addition of 6A and/or 19A-CRM197 conjugates on the immune response to the 10 pneumococcal polysaccharide conjugates common with Synflorix. The following exploratory analyses were added: • comparison of serotype-specific immune response elicited by the 11-valent and 12-valent pneumococcal conjugate vaccines versus the immune response elicited by Synflorix for the common serotypes, based on OPA GMT ratios for post-primary and post-booster timepoints and percentages of subjects with OPA titre >8 for post-primary timepoint. • comparison of serotype-specific immune response elicited by the 11-valent and 12-valent pneumococcal conjugate vaccines versus the immune response elicited by Synflorix for the common serotypes and by Prevenar 13 for the additional serotypes 6A and 19A, based on antibody GMC ratios and OPA GMT ratios for post-booster timepoint. • comparison of the immune response to serotypes 6A and 19A elicited by the 11-valent and 12-valent pneumococcal conjugate vaccines versus the lowest response elicited by Synflorix for any of the 10 vaccine serotypes, based on percentages of subjects reaching antibody concentrations/OPA titres above defined threshold for post-primary timepoint and antibody GMC/OPA GMT ratios for post-primary and post-booster timepoints.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Opsonophagocytic Activity results against pneumococcal serotype-19A and booster ELISA 6A results were not available at the time of writing this summary. The summary will be updated when they become available.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Antibody concentrations against pneumococcal serotypes during the Primary Phase of the study

Primary: Antibody concentrations against pneumococcal serotypes during the Primary Phase of the study

Primary: Percentage (%) of subjects (Synflorix and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during the primary phase

Primary: Percentage (%) of subjects (Synflorix and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during the primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 11Pn Groups) for pneumococcal serotypes during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 11Pn Groups) for pneumococcal serotypes during primary phase

Primary: Percentage (%) of subjects (Prevnar13 and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for ANTI-19A pneumococcal serotype during primary phase

Primary: Percentage (%) of subjects (Prevnar13 and 11Pn groups) with antibody concentration ≥ 0.2 μg/mL for ANTI-19A pneumococcal serotype during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 11Pn Groups) for ANTI-19A pneumococcal serotype during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 11Pn Groups) for ANTI-19A pneumococcal serotype during primary phase

Primary: Percentage (%) of subjects (Synflorix and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during primary phase

Primary: Percentage (%) of subjects (Synflorix and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for pneumococcal serotypes during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 12Pn Groups) for pneumococcal serotypes during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Synflorix and 12Pn Groups) for pneumococcal serotypes during primary phase

Primary: Percentage (%) of subjects (Prevnar13 and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for anti-6A and anti-19A pneumococcal serotypes during primary phase

Primary: Percentage (%) of subjects (Prevnar13 and 12Pn groups) with antibody concentration ≥ 0.2 μg/mL for anti-6A and anti-19A pneumococcal serotypes during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 12Pn Groups) for anti-6A and anti-19A pneumococcal serotypes during primary phase

Primary: Adjusted Geometric Mean Concentrations (GMC) (Prevnar13 and 12Pn Groups) for anti-6A and anti-19A pneumococcal serotypes during primary phase

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Primary Phase of the study

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Primary Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Primary Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Primary Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Booster Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited local symptoms during the Booster Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Primary Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Primary Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Booster Phase of the study

Secondary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms with relationship to vaccination, during the Booster Phase of the study

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Primary Phase of the study

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Primary Phase of the study

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Booster Phase of the study

Secondary: Number of subjects with any unsolicited adverse events (AEs) during the Booster Phase of the study

Secondary: Number of subjects with any serious adverse events (SAEs) during the Primary Phase of the study

Secondary: Number of subjects with any serious adverse events (SAEs) during the Primary Phase of the study

Secondary: Number of subjects with any serious adverse events (SAEs) during the entire duration of the study

Secondary: Number of subjects with any serious adverse events (SAEs) during the entire duration of the study

Secondary: Antibody concentrations against pneumococcal serotypes during the Booster Phase of the study

Secondary: Antibody concentrations against pneumococcal serotypes during the Booster Phase of the study

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Primary Phase of the study

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Primary Phase of the study

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Booster Phase of the study

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes during the Booster Phase of the study

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Booster Phase of the study

Secondary: Concentrations of antibodies against protein D (Anti-PD) during the Booster Phase of the study

Secondary: Antibody concentrations against pneumococcal serotype 6A during the Booster Phase of the study

Secondary: Antibody concentrations against pneumococcal serotype 6A during the Booster Phase of the study

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Primary Phase

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Primary Phase

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Booster Phase

Secondary: Titers for opsonophagocytic activity against pneumococcal serotypes 19A during the Booster Phase

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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