Download PDF

Clinical Trial Results:
A phase III randomized, single-blind, controlled study to demonstrate the non-inferiority of co-administration of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine with Pediacel versus co-administration with Infanrix hexa, when administered to infants as a three-dose primary vaccination course during the first six months of life and as a booster dose at 11-13 months of age.

Summary
EudraCT number	2007-004002-26
Trial protocol	NL
Global end of trial date	01 Dec 2010

Results information
Results version number	v3(current)
This version publication date	14 May 2023
First version publication date	19 Jun 2015
Other versions	v1 , v2
Version creation reason	Correction of full data set Correction of full data set and alignment between registries.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

110142, 111053

ISRCTN number

US NCT number

NCT00652951

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, 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

12 Dec 2011

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 May 2009

Global end of trial reached?

Yes

Global end of trial date

01 Dec 2010

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that GSK Biologicals’ 10 valent pneumococcal conjugate vaccine (Synflorix) when co-administered with Pediacel is non-inferior to co-administration with Infanrix hexa, in terms of immune response to the 10 pneumococcal vaccine serotypes and to protein D, when administered as a three-dose primary vaccination course. Criteria for non-inferiority: For each of the 10 pneumococcal vaccine serotypes and protein D, non-inferiority will be demonstrated if the upper limit of the 2-sided 95% CI of the geometric mean concentrations (GMCs) ratio between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), is lower than 2.

Protection of trial subjects

All subjects were supervised for 30 min after vaccination/product administration with appropriate medical treatment readily available in case of a rare anaphylactic reaction. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Also, all Intramuscular injections were administered into the anterolateral region of the thigh or into the deltoid. The buttock was not used for administration of vaccines because of the potential risk of injury to the sciatic nerve and the risk of decreased immunogenicity because of inadvertent subcutaneous injection or injection into deep fat tissue. For all intramuscular injections, the needle was selected long enough to reach the muscle mass and prevent vaccine from seeping into subcutaneous tissue, but not so long as to involve underling nerves and blood vessels or bone. Vaccinators were familiar with the anatomy of the area into which they are injecting vaccine. When appropriate, an individual decision on needle size and site of injection was made for each person on the basis of age, and the size of the muscle. Subjects were followed-up for 31 days after the last vaccination/product administration for adverse events following vaccination. Subjects were also followed during the entire study period for serious adverse events (SAEs).

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Apr 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 780

Worldwide total number of subjects

780

EEA total number of subjects

780

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)

780

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study included a Primary (PRI) Phase, up to Month 3, followed by a Booster (BST) Phase, up to Month 9.

Screening details

At screening the following was performed: informed consent was obtained and signed from subjects’ parents/guardians, check for inclusion/exclusion criteria and contraindications/precautions was performed as regards to vaccination, and medical history of subjects was collected. Subjects’ pre-vaccination body temperature was evaluated.

Period 1 title

Primary Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Synflorix + Infanrix hexa Group

Arm description

Subjects received 3 doses of Synflorix vaccine co-administered with Infanrix hexa at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (Synflorix) or left (Infanrix hexa) thigh or deltoid.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn-PD-DiT, 10Pn, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

DTPa-HBV-IPV/Hib

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Synflorix + Pediacel Group

Arm description

Subjects received 3 doses of Synflorix vaccine co-administered with Pediacel at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (Synflorix) or left (Pediacel) thigh or deltoid.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn-PD-DiT, 10Pn, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Pediacel

Investigational medicinal product code

DTPa-IPV-Hib

Other name

DTPa-IPV-Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Prevenar + Pediacel Group

Arm description

Subjects received 3 doses of Prevenar co-administered with Pediacel vaccine at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (Prevenar) or left (Pediacel) thigh or deltoid.

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

7Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Pediacel

Investigational medicinal product code

DTPa-IPV-Hib

Other name

DTPa-IPV-Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Number of subjects in period 1	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Started	260	260	260
Completed	260	260	260

Period 2 title

Booster Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Synflorix + Infanrix hexa Group

Arm description

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn-PD-DiT, 10Pn, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

DTPa-HBV-IPV/Hib

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Synflorix + Pediacel Group

Arm description

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn-PD-DiT, 10Pn, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Pediacel

Investigational medicinal product code

DTPa-IPV-Hib

Other name

DTPa-IPV-Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Prevenar + Pediacel Group

Arm description

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

7Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the right thigh or deltoid.

Investigational medicinal product name

Pediacel

Investigational medicinal product code

DTPa-IPV-Hib

Other name

DTPa-IPV-Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses at 2, 3 and 4 months of age (Study Months 0, 1, 2) followed by a booster dose between 11 and 13 months of age (Study Month 9). Vaccine was administered in the left thigh or deltoid.

Number of subjects in period 2 ^[1]	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Started	257	259	258
Completed	256	258	258
Not completed	1	1	0
Adverse event, non-fatal	-	1	-
Not specified	1	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all study participants returned in time for every study visit, but they were allowed to continue the study nonetheless. The number of participants who started each study period depends on the actual rate of return of the subjects.

Baseline characteristics

Top of page

Reporting group title

Synflorix + Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix + Pediacel Group

Reporting group description

Reporting group title

Prevenar + Pediacel Group

Reporting group description

Reporting group values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group	Total
Number of subjects	260	260	260	780
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	260	260	260	780
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	7.4 ( 1.2 )	7.6 ( 1.29 )	7.6 ( 1.26 )	-
Gender categorical
Units: Subjects
Female	118	130	136	384
Male	142	130	124	396

End points

Top of page

Reporting group title

Synflorix + Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix + Pediacel Group

Reporting group description

Reporting group title

Prevenar + Pediacel Group

Reporting group description

Reporting group title

Synflorix + Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix + Pediacel Group

Reporting group description

Reporting group title

Prevenar + Pediacel Group

Reporting group description

Primary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) - Primary vaccination

Top of page

End point title

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) - Primary vaccination

End point description

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were measured by 22F-inhibition Enzyme-Linked ImmunSorbent Assay (ELISA); presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was greater than or equal to (≥) 0.05 μg/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Primary

End point timeframe

At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	194	189	192
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-1 (N=181;178;178)	1.17 (1.02 to 1.33)	1.31 (1.16 to 1.48)	0.03 (0.03 to 0.03)
Anti-4 (N=192;185;191)	1.61 (1.41 to 1.84)	1.59 (1.38 to 1.83)	2.44 (2.19 to 2.73)
Anti-5 (N=187;181;178)	2.11 (1.88 to 2.37)	2.16 (1.92 to 2.43)	0.03 (0.03 to 0.03)
Anti-6B (N=177;174;180)	0.33 (0.26 to 0.4)	0.35 (0.28 to 0.43)	0.41 (0.34 to 0.51)
Anti-7F (N=192;187;183)	1.7 (1.52 to 1.9)	1.77 (1.57 to 1.99)	0.04 (0.03 to 0.04)
Anti-9V (N=185;186;187)	1.4 (1.2 to 1.63)	1.47 (1.29 to 1.68)	2.14 (1.91 to 2.4)
Anti-14 (N=192;187;192)	3.38 (2.99 to 3.81)	3.33 (2.93 to 3.78)	3.64 (3.24 to 4.1)
Anti-18C (N=194;189;191)	1.73 (1.45 to 2.05)	1.07 (0.92 to 1.25)	2.1 (1.83 to 2.4)
Anti-19F (N=189;183;189)	2.07 (1.73 to 2.48)	1.96 (1.64 to 2.34)	3.04 (2.71 to 3.42)
Anti-23F (N=179;175;184)	0.5 (0.41 to 0.6)	0.54 (0.44 to 0.66)	1.24 (1.04 to 1.47)

Immune response non-inferiority - serotype 1

Statistical analysis description

The 2-sided 95% confidence interval (CI) of the geometric mean concentration (GMC) ratio between the Synflorix + Infanrix hexa and Synflorix + Pediacel groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), at one month after Dose 3 of pneumococcal vaccine, was computed for each of the 10 pneumococcal vaccine serotypes and protein D. This statistical method concerns pneumococcal vaccine serotype 1.

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

GMC ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.07

Notes
[1] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% confidence interval (CI) of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 1.

Immune response non-inferiority - serotype 4

Statistical analysis description

The 2-sided 95% CI of the geometric mean concentration (GMC) ratio between the Synflorix + Infanrix hexa and Synflorix + Pediacel groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), at one month after Dose 3 of pneumococcal vaccine, was computed for each of the 10 pneumococcal vaccine serotypes and protein D. This statistical method concerns pneumococcal vaccine serotype 4.

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

GMC ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.23

Notes
[2] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 4.

Immune response non-inferiority - serotype 5

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

GMC ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.15

Notes
[3] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 5.

Immune response non-inferiority - serotype 6B

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

GMC ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.26

Notes
[4] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 6B.

Immune response non-inferiority - serotype 7F

Statistical analysis description

The 2-sided 95% CI of the geometric mean concentration (GMC) ratio between the Synflorix + Infanrix hexa and Synflorix + Pediacel Group groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), at one month after Dose 3 of pneumococcal vaccine, was computed for each of the 10 pneumococcal vaccine serotypes and protein D. This statistical method concerns pneumococcal vaccine serotype 7F.

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Notes
[5] - Non-inferiority criteria: The upper limit of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group Group), was lower than 2 for the pneumococcal vaccine serotype 7F.

Immune response non-inferiority - serotype 9V

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

GMC ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.16

Notes
[6] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 9V.

Immune response non-inferiority - serotype 14

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

GMC ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.21

Notes
[7] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 14.

Immune response non-inferiority - serotype 18C

Statistical analysis description

The 2-sided 95% CI of the geometric mean concentration (GMC) ratio between the Synflorix + Infanrix hexa and Synflorix + Pediacel groups (Synflorix + Infanrix hexa Group over), at one month after Dose 3 of pneumococcal vaccine, was computed for each of the 10 pneumococcal vaccine serotypes and protein D. This statistical method concerns pneumococcal vaccine serotype 18C.

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Regression, Cox

Parameter type

GMC ratio

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

2.03

Notes
[8] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 18C.

Immune response non-inferiority - serotype 19F

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

GMC ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.36

Notes
[9] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 19F.

Immune response non-inferiority - serotype 23F

Statistical analysis description

The 2-sided 95% CI of the geometric mean concentration (GMC) ratio between the Synflorix + Infanrix hexa Group and Synflorix + Pediacel groups (Synflorix + Infanrix hexa Group Group over Synflorix + Pediacel Group), at one month after Dose 3 of pneumococcal vaccine, was computed for each of the 10 pneumococcal vaccine serotypes and protein D. This statistical method concerns pneumococcal vaccine serotype 23F.

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

GMC ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.23

Notes
[10] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group Group over Synflorix + Pediacel Group), was lower than 2 for the pneumococcal vaccine serotype 23F.

Primary: Antibody concentration against protein D (PD) - Primary vaccination

Top of page

End point title

Antibody concentration against protein D (PD) - Primary vaccination

End point description

Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Primary

End point timeframe

At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	195	189	182
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD	1580 (1409.5 to 1771.1)	1743 (1560.2 to 1947.2)	69.7 (63 to 77.1)

Immune response non-inferiority - protein D

Statistical analysis description

Comparison groups

Synflorix + Infanrix hexa Group v Synflorix + Pediacel Group

Number of subjects included in analysis

384

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

GMC ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.06

Notes
[11] - Non-inferiority criteria: The upper limit (UL) of the 2-sided 95% CI of the GMC ratio for between groups (Synflorix + Infanrix hexa Group over Synflorix + Pediacel Group), was lower than 2 for protein D.

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Primary vaccination

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Primary vaccination

End point description

Antibody concentrations against the pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	194	189	192
Units: Subjects
Anti-1 (N=181;178;178)	174	176	5
Anti-4 (N=192;185;191)	188	180	189
Anti-5 (N=187;181;178)	187	179	0
Anti-6B (N=177;174;180)	122	113	124
Anti-7F (N=192;187;183)	190	186	11
Anti-9V (N=185;186;187)	176	181	184
Anti-14 (N=192;187;192)	191	187	192
Anti-18C (N=194;189;191)	183	178	187
Anti-19F (N=189;183;189)	180	174	189
Anti-23F (N=179;175;184)	134	133	171

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary vaccination

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary vaccination

End point description

Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	139	135	132
Units: Titers
geometric mean (confidence interval 95%)
Opsono-1 (N=132;126;125)	20.7 (15.6 to 27.6)	20.8 (15.8 to 27.4)	4.7 (4.1 to 5.2)
Opsono-4 (N=133;132;129)	592.9 (475.9 to 738.7)	600.4 (492.2 to 732.3)	838.4 (718.7 to 978.2)
Opsono-5 (N=138;134;132)	54.8 (44 to 68.4)	60.1 (48.2 to 74.8)	4.2 (3.9 to 4.6)
Opsono-6B (N=129;130;123)	261.3 (176 to 388)	296.4 (198 to 443.7)	633 (419 to 956.4)
Opsono-7F (N=130;127;114)	2063.3 (1691.7 to 2516.6)	2136.1 (1707.9 to 2671.5)	18.4 (12.1 to 28)
Opsono-9V (N=132;129;125)	863.6 (687.6 to 1084.7)	1277.7 (1053.3 to 1550.1)	1194 (1009.5 to 1412.1)
Opsono-14 (N=134;135;127)	990.4 (820.6 to 1195.5)	1086.4 (899.6 to 1311.9)	1373.3 (1040.4 to 1812.7)
Opsono-18C (N=133;129;129)	122.6 (89.4 to 168.2)	84.2 (60.9 to 116.5)	213.6 (163.6 to 278.8)
Opsono-19F (N=137;133;130)	133 (98.1 to 180.2)	143.8 (108.6 to 190.3)	39.2 (30.6 to 50.4)
Opsono-23F (N=139;133;130)	847.4 (626.5 to 1146.3)	1089 (800.2 to 1482)	3703.4 (3119.4 to 4396.8)

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary vaccination

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary vaccination

End point description

Antibody concentrations against the cross- reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	185	177	183
Units: Subjects
Anti-6A (N=185;176;183)	58	51	41
Anti-19A (N=180;177;180	56	50	40

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Primary vaccination

Top of page

End point title

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Primary vaccination

End point description

Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations (Anti-6A and -19A) were measured by 22F-inhibition ELISA; presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	185	177	183
Units: µg/mL
geometric mean (confidence interval 65%)
Anti-6A (N=185;176;183)	0.1 (0.08 to 0.12)	0.1 (0.09 to 0.12)	0.08 (0.06 to 0.09)
Anti-19A (N=180;177;180)	0.1 (0.09 to 0.13)	0.09 (0.08 to 0.11)	0.08 (0.07 to 0.1)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Primary vaccination

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Primary vaccination

End point description

Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off of 8. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	135	129	130
Units: Titres
geometric mean (confidence interval 95%)
Opsono-6A (N=128;120;121)	23.2 (16.1 to 33.6)	25.4 (17.1 to 37.8)	33 (21.4 to 50.8)
Opsono-19A (N=135;129;130)	9 (6.9 to 11.7)	8 (6.3 to 10.2)	4.9 (4.4 to 5.4)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Primary vaccination

Top of page

End point title

Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Primary vaccination

End point description

Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). The seropositivity cut-off value was greater than or equal to (≥) 0.1 IU/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	187	180	189
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-diphteria (N=185;176;187)	1.475 (1.307 to 1.664)	1.078 (0.939 to 1.237)	1.077 (0.949 to 1.222)
Anti-tetanus (N=187;180;189)	2.873 (2.622 to 3.147)	1.702 (1.528 to 1.897)	0.934 (0.837 to 1.043)

No statistical analyses for this end point

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Primary vaccination

Top of page

End point title

Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Primary vaccination

End point description

Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off value was ≥ 0.15 µg/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	189	179	188
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP (N=189;179;188)	2.139 (1.766 to 2.59)	4.796 (3.829 to 6.007)	2.219 (1.724 to 2.857)

No statistical analyses for this end point

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Primary vaccination

Top of page

End point title

Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Primary vaccination

End point description

Anti-PT, anti-FHA and anti-PRN antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value was ≥ 5 EL.U/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	187	180	188
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT (N=187;180;188)	42.7 (39.1 to 46.6)	36.4 (33.4 to 39.8)	40.1 (37 to 43.6)
Anti-FHA (N=183;172;183)	145.6 (130.4 to 162.5)	100.8 (89.6 to 113.5)	100.5 (89.9 to 112.4)
Anti-PRN (N=187;180;188)	97.6 (86.8 to 109.7)	40.1 (34.8 to 46.1)	45.1 (39.3 to 51.7)

No statistical analyses for this end point

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Primary vaccination

Top of page

End point title

Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Primary vaccination

End point description

Antibody concentrations were presented as GMCs and expressed in mIU/mL. A seroprotected subject was a subject whose antibody ChemiLuminescence ImmunoAssay(CLIA) concentration was ≥10 mIU/mL. Note: investigations on the quality of some serology assays revealed that the anti-HBs ELISA overestimated concentration between 10-100 mIU/mL while values >100 mIU/mL were confirmed valid. All available samples at one month post-dose III and month post-dose IV timepoints for which the anti-HBs antibody concentration was between 10-100 mIU/mL by in-house ELISA, were retested by the commercial assay Centaur, an FDA-approved and CE-marked CLIA with a cut-off defining seropositivity of 6.2 mIU/mL. Anti-HBs seroprotection was redefined as in-house ELISA concentration >100 mIU/mL or CLIA concentration >10 mIU/mL. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	111	112	113
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs (N=111;112;113)	356.9 (279.4 to 455.8)	14 (11.6 to 16.9)	11.5 (9.8 to 13.5)

No statistical analyses for this end point

Secondary: Anti-polio types 1, 2 and 3 titers - Primary vaccination

Top of page

End point title

Anti-polio types 1, 2 and 3 titers - Primary vaccination

End point description

Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8. The Primary ATP cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component post-dose III.

End point type

Secondary

End point timeframe

At Month 3, one month after the administration of the third vaccine dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	156	150	149
Units: Titers
geometric mean (confidence interval 95%)
Anti-polio 1 (N=155;150;149)	27.2 (21.7 to 34.1)	16 (13 to 19.7)	18.1 (14.8 to 22.1)
Anti-polio 2 (N=156;149;149)	37.1 (29.1 to 47.4)	29 (23 to 36.6)	23.2 (18.5 to 29.1)
Anti-polio 3 (N=156;148;149)	47.3 (35.8 to 62.4)	34.2 (27 to 43.4)	26.7 (21.5 to 33)

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Booster vaccination

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Booster vaccination

End point description

Antibody concentrations against the pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	190	198	202
Units: Subjects
Anti-1, PRE(N=178;185;198)	84	92	6
Anti-4, PRE (N=174;181;194)	136	147	148
Anti-5, PRE (N=181;181;198)	142	152	3
Anti-6B, PRE (N=175;180;192)	117	127	62
Anti-7F, PRE(N=176;181;195)	165	164	5
Anti-9V, PRE(N=180;180;196)	168	168	176
Anti-14, PRE (N=183;184;199)	170	172	190
Anti-18C, PRE (N=179;181;194)	152	143	151
Anti-19F, PRE(N=172;177;197)	149	157	109
Anti-23F, PRE (N=180;182;196)	123	140	108
Anti-1, POST(N=187;196;199)	187	195	7
Anti-4, POST (N=187;194;198)	187	194	198
Anti-5, POST (N=186;191;195)	185	191	4
Anti-6B, POST (N=186;193;199)	176	181	192
Anti-7F, POST (N=189;198;199)	189	198	8
Anti-9V, POST (N=188;197;202)	188	197	202
Anti-14, POST (N=190;198;201)	190	197	198
Anti-18C, POST (N=189;197;200)	188	196	200
Anti-19F, POST(N=183;194;196)	180	191	196
Anti-23F, POST (N=185;194;199)	179	190	194

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - Booster vaccination

Top of page

End point title

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - Booster vaccination

End point description

Anti-pneumococcal serotype 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	190	198	202
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-1, PRE(N=178;185;198)	0.2 (0.17 to 0.22)	0.22 (0.19 to 0.26)	0.03 (0.03 to 0.04)
Anti-4, PRE (N=174;181;194)	0.39 (0.34 to 0.46)	0.43 (0.37 to 0.5)	0.38 (0.34 to 0.43)
Anti-5, PRE (N=181;181;198)	0.41 (0.36 to 0.47)	0.42 (0.37 to 0.48)	0.03 (0.03 to 0.04)
Anti-6B, PRE (N=175;180;192)	0.3 (0.25 to 0.36)	0.32 (0.27 to 0.38)	0.13 (0.11 to 0.16)
Anti-7F, PRE(N=176;181;195)	0.6 (0.54 to 0.68)	0.62 (0.55 to 0.71)	0.03 (0.03 to 0.03)
Anti-9V, PRE(N=180;180;196)	0.68 (0.6 to 0.78)	0.76 (0.66 to 0.89)	0.55 (0.49 to 0.62)
Anti-14, PRE (N=183;184;199)	1.06 (0.9 to 1.26)	1.14 (0.95 to 1.36)	1.55 (1.35 to 1.79)
Anti-18C, PRE (N=179;181;194)	0.58 (0.49 to 0.68)	0.43 (0.36 to 0.5)	0.4 (0.35 to 0.45)
Anti-19F, PRE(N=172;177;197)	0.79 (0.64 to 0.99)	0.9 (0.73 to 1.11)	0.31 (0.25 to 0.37)
Anti-23F, PRE (N=180;182;196)	0.33 (0.27 to 0.39)	0.38 (0.32 to 0.46)	0.26 (0.22 to 0.3)
Anti-1, POST(N=187;196;199)	2.16 (1.89 to 2.46)	2.5 (2.19 to 2.86)	0.03 (0.03 to 0.04)
Anti-4, POST (N=187;194;198)	3.04 (2.7 to 3.42)	3.29 (2.89 to 3.73)	4.01 (3.53 to 4.56)
Anti-5, POST (N=186;191;195)	3.27 (2.9 to 3.7)	3.27 (2.9 to 3.68)	0.04 (0.03 to 0.04)
Anti-6B, POST (N=186;193;199)	1.45 (1.23 to 1.71)	1.41 (1.19 to 1.67)	2.52 (2.15 to 2.96)
Anti-7F, POST (N=189;198;199)	3.79 (3.4 to 4.23)	4.06 (3.63 to 4.54)	0.03 (0.03 to 0.04)
Anti-9V, POST (N=188;197;202)	3.96 (3.58 to 4.39)	4.23 (3.78 to 4.74)	6.05 (5.38 to 6.8)
Anti-14, POST (N=190;198;201)	4.59 (4.06 to 5.19)	4.95 (4.38 to 5.6)	7.31 (6.37 to 8.39)
Anti-18C, POST (N=189;197;200)	6.36 (5.56 to 7.27)	4.63 (4.09 to 5.25)	5.08 (4.47 to 5.78)
Anti-19F, POST(N=183;194;196)	5.45 (4.72 to 6.3)	5.8 (5.04 to 6.68)	2.4 (2.14 to 2.7)
Anti-23F, POST (N=185;194;199)	2.32 (1.98 to 2.71)	2.6 (2.24 to 3.02)	5.32 (4.49 to 6.31)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster vaccination

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster vaccination

End point description

Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	156	154	168
Units: Titers
geometric mean (confidence interval 95%)
Opsono-1, PRE (N=149;152;168)	5.5 (4.7 to 6.4)	5.6 (4.7 to 6.7)	5 (4.4 to 5.8)
Opsono-4, PRE (N=145;150;164)	11.3 (8.6 to 14.9)	15.3 (11.3 to 20.6)	12.3 (9.3 to 16.2)
Opsono-5, PRE (N=148;151;166)	7.2 (6.1 to 8.5)	7 (6 to 8.1)	4.3 (4 to 4.6)
Opsono-6B, PRE (N=141;138;153)	52 (34.8 to 77.7)	96.7 (63.1 to 148)	27.4 (18.6 to 40.3)
Opsono-7F, PRE (N=146;150;146)	818.9 (642.2 to 1044.3)	754.3 (598.4 to 950.8)	138.1 (91.2 to 209.2)
Opsono-9V, PRE (N=143;147;159)	267.2 (212.7 to 335.8)	338.7 (264.8 to 433.2)	149.5 (112.4 to 198.9)
Opsono-14, PRE (N=143;144;161)	117.3 (82.9 to 165.9)	142.5 (101.3 to 200.4)	156 (114.5 to 212.5)
Opsono-18C, PRE (N=139;148;162)	8.2 (6.2 to 10.8)	6.8 (5.3 to 8.5)	7 (5.7 to 8.7)
Opsono-19F, PRE (N=149;149;167)	13.8 (10.6 to 18.1)	15.4 (11.8 to 20.2)	7.8 (6.2 to 9.9)
Opsono-23F, PRE (N=143;143;162)	314.1 (198.6 to 496.7)	350.4 (229.8 to 534.2)	338.9 (219.9 to 522.3)
Opsono-1, POST (N=156;154;164)	208.8 (160.6 to 271.7)	221.4 (165.1 to 297)	4.6 (4.2 to 5.1)
Opsono-4, POST (N=155;152;164)	1046.8 (865.8 to 1265.7)	1121.6 (909.4 to 1383.3)	2335.8 (1946.3 to 2803.3)
Opsono-5, POST (N=152;151;164)	149.3 (119.2 to 187)	132.4 (103.8 to 168.9)	4.1 (4 to 4.3)
Opsono-6B, POST (N=153;149;160)	681.4 (514.6 to 902.1)	763.3 (581.9 to 1001.3)	1807.5 (1408 to 2320.3)
Opsono-7F, POST (N=154;152;153)	3936.5 (3413.2 to 4540)	3976 (3390.2 to 4663.1)	129.1 (85.9 to 193.9)
Opsono-9V, POST (N=153;151;163)	2512.9 (2213.1 to 2853.2)	2257.6 (1974.3 to 2581.5)	3889.5 (3260.1 to 4640.2)
Opsono-14, POST (N=154;154;164)	1534.2 (1290.9 to 1823.3)	1896.3 (1591.3 to 2259.7)	1867.9 (1540.5 to 2265.1)
Opsono-18C, POST (N=153;152;159)	720.7 (597.5 to 869.4)	385.9 (303.5 to 490.8)	660.4 (520.9 to 837.3)
Opsono-19F, POST (N=153;149;164)	435.7 (336.3 to 564.5)	475.4 (377.8 to 598.1)	123.2 (95.9 to 158.2)
Opsono-23F, POST (N=152;154;164)	2895.4 (2276.1 to 3683.1)	2895.3 (2419.3 to 3465)	12418.7 (10171.8 to 15161.9)

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster vaccination

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster vaccination

End point description

Antibody concentrations against the cross-reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	187	196	201
Units: Subjects
Anti-6A, PRE (N=181;185;193)	50	56	28
Anti-19A, PRE (N=182;184;199)	61	63	29
Anti-6A, POST (N=187;196;201)	135	142	160
Anti-19A, POST (N=187;195;200)	130	139	97

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Booster vaccination

Top of page

End point title

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Booster vaccination

End point description

Anti-pneumococcal cross-reactive serotype 6A and 19A antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	187	196	201
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A, PRE (N=181;185;193)	0.1 (0.09 to 0.12)	0.11 (0.09 to 0.13)	0.06 (0.05 to 0.07)
Anti-19A, PRE (N=182;184;199)	0.12 (0.1 to 0.15)	0.12 (0.09 to 0.14)	0.06 (0.05 to 0.07)
Anti-6A, POST (N=187;196;201)	0.45 (0.36 to 0.55)	0.49 (0.4 to 0.61)	0.71 (0.58 to 0.88)
Anti-19A, POST (N=187;195;200)	0.5 (0.39 to 0.63)	0.52 (0.41 to 0.66)	0.21 (0.17 to 0.25)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Booster vaccination

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Booster vaccination

End point description

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	151	148	167
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A, PRE (N=128;135;151)	23.3 (15.7 to 34.6)	30.7 (20.8 to 45.2)	15.5 (11.1 to 21.6)
Opsono-19A, PRE (N=148;148;167)	5.7 (4.6 to 7)	5.5 (4.6 to 6.5)	5.5 (4.6 to 6.5)
Opsono-6A, POST (N=145;142;160)	143.3 (99.1 to 207.3)	197.1 (138 to 281.3)	493.3 (357.1 to 681.6)
Opsono-19A, POST (N=151;148;162)	34.9 (24.8 to 49.2)	24.6 (17.7 to 34.3)	7.7 (6.2 to 9.5)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (Anti-PD) - Booster vaccination

Top of page

End point title

Concentrations of antibodies against protein D (Anti-PD) - Booster vaccination

End point description

Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	189	198	201
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD, PRE (N=182;189;195)	421 (370.3 to 478.5)	520.5 (455.8 to 594.3)	80.8 (73.1 to 89.4)
Anti-PD, POST (N=189;198;201)	1715 (1510.3 to 1947.5)	1936.8 (1710.5 to 2193.2)	84.1 (76 to 93.1)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Booster vaccination

Top of page

End point title

Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Booster vaccination

End point description

Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). The seropositivity cut-off value was greater than or equal to (≥) 0.1 IU/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	186	194	197
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-diphteria, PRE (N=175;179;192)	0.235 (0.205 to 0.27)	0.232 (0.203 to 0.264)	0.266 (0.235 to 0.301)
Anti-tetanus, PRE (N=175;180;193)	0.728 (0.656 to 0.809)	0.536 (0.477 to 0.603)	0.232 (0.202 to 0.267)
Anti-diphteria, POST (N=186;194;197)	4.061 (3.601 to 4.58)	3.226 (2.866 to 3.632)	4.882 (4.425 to 5.386)
Anti-tetanus, POST (N=186;194;197)	8.628 (7.867 to 9.462)	5.989 (5.461 to 6.568)	3.248 (2.859 to 3.69)

No statistical analyses for this end point

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Booster vaccination

Top of page

End point title

Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Booster vaccination

End point description

Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off value was ≥ 0.15 µg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	184	192	197
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-PRP, PRE (N=174;179;193)	0.475 (0.386 to 0.585)	0.855 (0.682 to 1.072)	0.371 (0.298 to 0.461)
Anti-PRP, POST (N=184;192;197)	19.331 (16.144 to 23.147)	39.383 (32.617 to 47.551)	23.676 (18.944 to 29.591)

No statistical analyses for this end point

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Booster vaccination

Top of page

End point title

Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Booster vaccination

End point description

Anti-PT, anti-FHA and anti-PRN antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value was ≥ 5 EL.U/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	186	194	197
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT, PRE (N=174;176;189)	7.4 (6.6 to 8.4)	6 (5.4 to 6.7)	6.6 (5.9 to 7.3)
Anti-FHA, PRE (N=175;179;191)	34 (29.4 to 39.4)	35.3 (30.8 to 40.6)	34.7 (30.1 to 39.9)
Anti-PRN, PRE (N=175;179;192)	14.1 (12.3 to 16.2)	6.8 (5.9 to 7.9)	8.6 (7.4 to 10)
Anti-PT, POST (N=186;194;196)	53.5 (48.3 to 59.2)	47.4 (42.9 to 52.5)	54.8 (48.9 to 61.4)
Anti-FHA, POST (N=184;192;194)	343.5 (308 to 383.1)	135.7 (121.2 to 151.9)	140 (123.2 to 159.1)
Anti-PRN, POST (N=186;193;197)	281.7 (247.2 to 321)	97.8 (85.4 to 112)	106.4 (91.5 to 123.8)

No statistical analyses for this end point

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Booster vaccination

Top of page

End point title

Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Booster vaccination

End point description

Antibody concentrations were presented as GMCs and expressed in mIU/mL. A seroprotected subject was a subject whose antibody CLIA concentration was ≥10 mIU/mL. Note: investigations on the quality of some serology assays revealed that the anti-HBs ELISA overestimated concentration between 10-100 mIU/mL while values >100 mIU/mL were confirmed valid. Therefore, all available samples at one month post-dose III and one month post-dose IV timepoints for which the anti-HBs antibody concentration was between 10-100 mIU/mL by in-house ELISA, were retested by the commercial assay Centaur, an FDA-approved and CE-marked CLIA with a cut-off defining seropositivity of 6.2 mIU/mL. Anti-HBs seroprotection was redefined as in-house ELISA concentration >100 mIU/mL or CLIA concentration >10 mIU/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	125	124	135
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, PRE (121;124;135)	142.1 (113.4 to 178.1)	9.9 (8.8 to 11.2)	9.9 (8.8 to 11.2)
Anti-HBs, POST (125;123;135)	1981 (1552 to 2528.7)	8.6 (7.6 to 9.9)	8.5 (7.6 to 9.5)

No statistical analyses for this end point

Secondary: Anti-polio types 1, 2 and 3 titers - Booster vaccination

Top of page

End point title

Anti-polio types 1, 2 and 3 titers - Booster vaccination

End point description

Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

Prior to (PRE/Month 9) and one month after the administration of the booster dose (POST/Month 10)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	167	173	182
Units: Titers
geometric mean (confidence interval 95%)
Anti-polio 1, PRE (N=156;166;182)	8.3 (7 to 10)	7.3 (6.3 to 8.4)	7 (6.1 to 8)
Anti-polio 2, PRE (N=156;164;182)	13.4 (10.8 to 16.6)	10.6 (8.8 to 12.7)	10.4 (8.9 to 12.2)
Anti-polio 3, PRE (N=156;166;180)	11.3 (9.3 to 13.9)	9 (7.5 to 10.7)	8.7 (7.4 to 10.3)
Anti-polio 1, POST (N=166;173;170)	370.7 (289.8 to 474.2)	177.5 (135.8 to 231.9)	221.2 (171.5 to 285.3)
Anti-polio 2, POST (N=167;173;169)	710.8 (588 to 859.3)	338.8 (272.7 to 420.8)	481.4 (391 to 592.7)
Anti-polio 3, POST (N=167;172;170)	631.5 (495.7 to 804.4)	311.9 (240.4 to 404.6)	348.3 (263.6 to 460.2)

No statistical analyses for this end point

Secondary: Number of subjects with booster vaccine response against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies - Booster vaccination

Top of page

End point title

Number of subjects with booster vaccine response against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies - Booster vaccination

End point description

A booster responder to PT/FHA/PRN was defined as a subject with antibodies concentration ≥ 5 EL.U/mL against PT/FHA/PRN in subjects who were initially seronegative for anti-PT/FHA/PRN antibodies (i.e., subjects with anti-PT/FHA/PRN antibody concentrations < 5 EL.U/mL), or antibody concentration ≥ 2 fold the pre-vaccination antibody concentration in subjects who were initially seropositive (i.e., subjects with anti-PT/FHA/PRN antibody concentrations ≥ 5 EL.U/mL). All evaluable subjects, for whom assay results were available for the respective antigen both before and after booster vaccination. For Anti-PT and anti-FHA antigens, evaluable data were not available for 1 participant (Synflorix + Infanrix Hexa), 2 and 1 participants respectively (Synflorix + Pediacel), 2 and 3 participants (Prevenar + Pediacel).

End point type

Secondary

End point timeframe

One month after (Month 10) the administration of the booster dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	140	145	155
Units: Subjects
Anti-PT, S- seronegative (N=40;48;48)	40	47	48
Anti-PT, S+ seropositive (N=99;95;105)	95	94	98
Anti-FHA, S- seronegative (N=4;1;2)	4	1	2
Anti-FHA, S+ seropositive (N=135;143;150)	128	119	125
Anti-PRN, S- seronegative (N=18;56;53)	18	56	51
Anti-PRN, S+ seropositive (N=122;89;102)	122	88	101

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - 12 months after booster dose

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - 12 months after booster dose

End point description

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	166	169	177
Units: Subjects
Anti-1, M12 (N=163;166;173)	106	108	6
Anti-4, M12 (N=163;167;173)	101	102	130
Anti-5, M12 (N=163;163;170)	129	129	10
Anti-6B, M12 (N=162;164;173)	94	96	133
Anti-7F, M12 (N=163;165;170)	157	157	15
Anti-9V, M12 (N=165;168;173)	155	157	160
Anti-14, M12 (N=166;169;177)	149	156	173
Anti-18C, M12 (N=164;167;174)	160	155	161
Anti-19F, M12 (N=164;165;171)	158	158	134
Anti-23F, M12(N=162;166;172)	123	126	153

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - 12 months after booster dose

Top of page

End point title

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - 12 months after booster dose

End point description

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	166	169	177
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-1, M12 (N=163;166;173)	0.3 (0.26 to 0.35)	0.32 (0.28 to 0.38)	0.04 (0.03 to 0.04)
Anti-4, M12 (N=163;167;173)	0.25 (0.22 to 0.29)	0.29 (0.25 to 0.34)	0.36 (0.32 to 0.42)
Anti-5, M12 (N=163;163;170)	0.45 (0.39 to 0.53)	0.47 (0.39 to 0.55)	0.05 (0.04 to 0.05)
Anti-6B, M12 (N=162;164;173)	0.3 (0.25 to 0.36)	0.32 (0.26 to 0.4)	0.46 (0.38 to 0.56)
Anti-7F, M12 (N=163;165;170)	0.72 (0.63 to 0.81)	0.73 (0.64 to 0.84)	0.04 (0.03 to 0.05)
Anti-9V, M12 (N=165;168;173)	0.74 (0.63 to 0.88)	0.78 (0.66 to 0.91)	0.81 (0.7 to 0.94)
Anti-14, M12 (N=166;169;177)	0.73 (0.62 to 0.86)	0.85 (0.73 to 0.99)	1.28 (1.1 to 1.48)
Anti-18C, M12 (N=164;167;174)	1.03 (0.89 to 1.19)	0.64 (0.56 to 0.74)	0.66 (0.59 to 0.75)
Anti-19F, M12 (N=164;165;171)	1.48 (1.22 to 1.8)	1.46 (1.2 to 1.78)	0.76 (0.59 to 0.98)
Anti-23F, M12(N=162;166;172)	0.51 (0.41 to 0.63)	0.52 (0.42 to 0.63)	1.01 (0.83 to 1.24)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 months after booster dose

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 months after booster dose

End point description

Antibody concentrations against the cross-reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	159	152	165
Units: Titers
geometric mean (confidence interval 95%)
Opsono-1, M12 (N=159;150;162)	10.9 (8.5 to 14.1)	9.9 (7.8 to 12.5)	4.3 (3.9 to 4.7)
Opsono-4, M12 (N=154;147;160)	12 (9.1 to 15.9)	15.5 (11 to 21.7)	45.2 (30.8 to 66.5)
Opsono-5, M12 (N=159;152;165)	12.9 (10.4 to 16)	13.7 (11 to 17.1)	4.1 (3.9 to 4.3)
Opsono-6B, M12 (N=139;137;152)	77.7 (48.8 to 123.8)	137.6 (83.5 to 226.6)	220 (145.4 to 332.8)
Opsono-7F, M12 (N=142;136;143)	1982.9 (1568.8 to 2506.2)	2205.6 (1833.4 to 2653.4)	738.1 (549.8 to 990.7)
Opsono-9V, M12 (N=143;135;147)	465.9 (324.2 to 669.5)	470 (325.8 to 677.9)	476.2 (317.8 to 713.5)
Opsono-14, M12 (N=128;121;149)	93.1 (60 to 144.4)	151.6 (97.7 to 235.4)	238.7 (163.5 to 348.6)
Opsono-18C, M12 (N=135;133;151)	21.6 (15.2 to 30.6)	12.5 (8.9 to 17.6)	15.3 (10.9 to 21.3)
Opsono-19F, M12 (N=148;150;162)	31.1 (22.6 to 42.8)	32.9 (23.8 to 45.4)	15.1 (11 to 20.6)
Opsono-23F, M12 (N=146;140;161)	366.5 (218.3 to 615.3)	706.1 (443.5 to 1124.3)	3879.8 (2774.4 to 5425.5)

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 months after booster dose

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 months after booster dose

End point description

Antibody concentrations against the cross-reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	165	166	176
Units: Subjects
Anti-6A, M12 (N=163;166;174)	54	57	92
Anti-19A, M12 (N=165;166;176)	120	97	80

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - 12 months after booster dose

Top of page

End point title

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - 12 months after booster dose

End point description

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	165	166	176
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A, M12 (N=163;166;174)	0.14 (0.12 to 0.17)	0.15 (0.12 to 0.19)	0.22 (0.18 to 0.27)
Anti-19A, M12 (N=165;166; 176)	0.43 (0.35 to 0.53)	0.29 (0.23 to 0.36)	0.21 (0.16 to 0.27)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - 12 months after booster dose

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - 12 months after booster dose

End point description

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	150	146	158
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A, M12 (N=126;129;148)	21.6 (14.1 to 33.1)	24.8 (15.5 to 39.5)	56.5 (36.4 to 87.7)
Opsono-19A, M12 (N=150;146;158)	12.6 (9.5 to 16.7)	9.1 (7 to 11.9)	9.6 (7.1 to 12.9)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (Anti-PD) - 12 months after booster dose

Top of page

End point title

Concentrations of antibodies against protein D (Anti-PD) - 12 months after booster dose

End point description

Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. The Booster ATP cohort for immunogenicity included all evaluable subjects, for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination.

End point type

Secondary

End point timeframe

At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) (M12)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	168	170	178
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD, M12 (N=168;170;178)	332 (287.1 to 384)	423 (359.9 to 497.1)	81.4 (73.1 to 90.6)

No statistical analyses for this end point

Secondary: Number of subjects with positive cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the nasopharynx - Primary vaccination

Top of page

End point title

Number of subjects with positive cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the nasopharynx - Primary vaccination

End point description

Positive cultures of H. influenzae* (HI) and S. pneumoniae (SP) identified in the nasopharynx at each swab time point: one month post-Dose III (M3), M9 (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). *Data presented only include results from samples confirmed as positive for H. influenzae / Non-typeable H. influenzae after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

One month after the third dose (Month 3), prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	259	259
Units: Subjects
Any SP, Month 3 [N=260;259;259]	102	109	100
Any SP, Month 9 [N=255;259;258]	115	134	119
Any SP, Month 12 [N=256;258;257]	121	131	126
Any SP, Month 16 [N=256;258;258]	151	135	148
Any SP, Month 21 [N=255;257;257]	154	139	131
Any HI, Month 3 [N=259;258;258]	94	91	85
Any HI, Month 9 [N=254;258;256]	152	155	144
Any HI, Month 12 [N=260;258;257]	159	160	165
Any HI, Month 16 [N=252;258;256]	185	169	162
Any HI, Month 21 [N=254;255;254]	192	192	177

No statistical analyses for this end point

Secondary: Number of subjects with positive cultures of Streptococcus Pneumoniae vaccine seroptypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) in the nasopharynx - Primary vaccination

Top of page

End point title

Number of subjects with positive cultures of Streptococcus Pneumoniae vaccine seroptypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) in the nasopharynx - Primary vaccination

End point description

Positive cultures of S. pneumoniae (SP) identified in the nasopharynx at each swab time point: one month post-Dose III (M3), pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	259	259
Units: Subjects
S. pneumoniae, VS - M3 [N=260;259;259]	18	25	21
S. pneumoniae, VS - M9 [N=255;259;257]	16	20	18
S. pneumoniae, VS - M12 [N=256;258;257]	11	18	13
S. pneumoniae, VS - M16 [N=256;258;258]	15	12	12
S. pneumoniae, VS - M21 [N=255;257;257]	8	8	8
S. pneumoniae, CRS - M3 [N=260;259;259]	25	32	20
S. pneumoniae, CRS - M9 [N=255;259;257]	15	30	25
S. pneumoniae, CRS - M12 [N=256;258;257]	25	26	27
S. pneumoniae, CRS - M16 [N=256;258;258]	33	33	31
S. pneumoniae, CRS - M21 [N=255;257;257]	28	13	25
S. pneumoniae, OS - M3 [N=260;259;259]	45	40	51
S. pneumoniae, OS - M9 [N=255;259;257]	69	61	60
S. pneumoniae, OS - M12 [N=256;258;257]	74	69	70
S. pneumoniae, OS - M16 [N=256;258;258]	86	67	89
S. pneumoniae, OS - M21 [N=255;257;257]	97	81	80

No statistical analyses for this end point

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs - Primary vaccination

Top of page

End point title

Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs - Primary vaccination

End point description

Acquisition of new H. influenzae* (HI) and S. pneumoniae (SP) strains, identified in the nasopharynx at each swab time point: pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). *Data presented only include results from samples confirmed as positive for H. influenzae / Non-typeable H. influenzae after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	256	259	258
Units: Subjects
Any SP, M9 [N=255;259;258]	103	114	107
Any SP, M12 [N=256;258;257]	86	95	90
Any SP, M16 [N=256;258;258]	128	105	125
Any SP, M21 [N=255;257;257]	132	113	110
Any HI, M9 [N=254;258;256]	88	84	83
Any HI, M12 [N=256;258;257]	47	48	58
Any HI, M16 [N=252;258;256]	71	55	64
Any HI, M21 [N=254;255;254]	73	75	71

No statistical analyses for this end point

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae vaccine serotypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) identified in nasopharyngeal swabs - Primary vaccination

Top of page

End point title

Number of subjects with acquisition of new Streptococcus pneumoniae vaccine serotypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) identified in nasopharyngeal swabs - Primary vaccination

End point description

Acquisition of new S. pneumonia (SP) strains, identified in the nasopharynx at each swab time point: pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	256	259	258
Units: Subjects
S. pneumoniae, VS - M9 [N=255;259;257]	14	11	15
S. pneumoniae, VS - M12 [N=256;258;257]	8	9	8
S. pneumoniae, VS - M16 [N=256;258;258]	13	7	9
S. pneumoniae, VS - M21 [N=255;257;257]	4	7	6
S. pneumoniae, CRS - M9 [N=255;259;257]	13	26	20
S. pneumoniae, CRS - M12 [N=256;258;257]	19	15	20
S. pneumoniae, CRS - M16 [N=256;258;258]	27	25	24
S. pneumoniae, CRS - M21 [N=255;257;257]	22	8	18
S. pneumoniae, OS - M9 [N=255;259;257]	64	55	57
S. pneumoniae, OS - M12 [N=256;258;257]	52	59	52
S. pneumoniae, OS - M16 [N=256;258;258]	74	55	77
S. pneumoniae, OS - M21 [N=255;257;257]	87	69	69

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms - Primary vaccination

Top of page

End point title

Number of subjects with solicited local symptoms - Primary vaccination

End point description

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling spreading beyond (>) 30 millimeters from injection site. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	260	260
Units: Subjects
Any Pain, Dose 1 [N=260;260;260]	168	159	142
Grade 3 Pain, Dose 1 [N=260;260;260]	30	31	22
Any Redness, Dose 1 [N=260;260;260]	105	134	120
Grade 3 Redness, Dose 1 [N=260;260;260]	7	21	15
Any Swelling, Dose 1 [N=260;260;260]	140	145	113
Grade 3 Swelling, Dose 1 [N=260;260;260]	12	18	15
Any Pain, Dose 2 [N=259;260;260]	130	120	104
Grade 3 Pain, Dose 2 [N=259;260;260]	11	12	13
Any Redness, Dose 2 [N=259;260;260]	125	131	121
Grade 3 Redness, Dose 2 [N=259;260;260]	4	8	4
Any Swelling, Dose 2 [N=259;260;260]	143	135	125
Grade 3 Swelling, Dose 2 [N=259;260;260]	7	8	8
Any Pain, Dose 3 [N=260;259;260]	100	87	73
Grade 3 Pain, Dose 3 [N=260;259;260]	9	4	5
Any Redness, Dose 3 [N=260;259;260]	141	119	121
Grade 3 Redness, Dose 3 [N=260;259;260]	1	1	1
Any Swelling, Dose 3 [N=260;259;260]	142	133	118
Grade 3 Swelling, Dose 3 [N=260;259;260]	4	7	10
Any Pain, Across doses [N=260;260;260]	205	193	178
Grade 3 Pain, Across doses [N=260;260;260]	42	40	29
Any Redness, Across doses [N=260;260;260]	197	193	184
Grade 3 Redness, Across doses [N=260;260;260]	12	26	19
Any Swelling, Across doses [N=260;260;260]	205	199	179
Grade 3 Swelling, Across doses [N=260;260;260]	18	29	24

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms - Primary vaccination

Top of page

End point title

Number of subjects with solicited general symptoms - Primary vaccination

End point description

Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. Related symptom was defined as a general symptom assessed by the investigator as causally related to study vaccination. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	260	260
Units: Subjects
Any Drowsiness, Dose 1 [N=260;260;260]	183	164	164
Grade 3 Drowsiness, Dose 1 [N=260;260;260]	4	6	6
Related Drowsiness, Dose 1 [N=260;260;260]	178	160	160
Any Temperature, Dose 1 [N=260;260;260]	88	40	40
Grade 3 Temperature, Dose 1 [N=260;260;260]	0	0	0
Related Temperature, Dose 1 [N=260;260;260]	88	40	40
Any Irritability, Dose 1 [N=260;260;260]	190	180	180
Grade 3 Irritability, Dose 1 [N=260;260;260]	18	8	8
Related Irritability, Dose 1 [N=260;260;260]	186	173	173
Any Loss of appetite, Dose 1 [N=260;260;260]	88	87	87
Grade 3 Loss of appetite, Dose 1 [N=260;260;260]	3	1	1
Related Loss of appetite, Dose 1 [N=260;260;260]	65	84	84
Any Drowsiness, Dose 2 [N=259;260;260]	157	143	143
Grade 3 Drowsiness, Dose 2 [N=259;260;260]	5	1	1
Related Drowsiness, Dose 2 [N=259;260;260]	152	141	141
Any Temperature, Dose 2 [N=259;260;260]	82	60	60
Grade 3 Temperature, Dose 2 [N=259;260;260]	0	0	0
Related Temperature, Dose 2 [N=259;260;260]	81	59	59
Any Irritability, Dose 2 [N=259;260;260]	181	165	165
Grade 3 Irritability, Dose 2 [N=259;260;260]	14	5	5
Related Irritability, Dose 2 [N=259;260;260]	177	154	154
Any Loss of appetite, Dose 2 [N=259;260;260]	82	85	85
Grade 3 Loss of appetite, Dose 2 [N=259;260;260]	1	0	0
Related Loss of appetite, Dose 2 [N=259;260;260]	80	81	81
Any Drowsiness, Dose 3 [N=259;260;260]	127	118	118
Grade 3 Drowsiness, Dose 3 [N=260;259;260]	7	1	1
Related Drowsiness, Dose 3 [N=260;259;260]	124	115	115
Any Temperature, Dose 3 [N=260;259;260]	70	38	38
Grade 3 Temperature, Dose 3 [N=260;259;260]	0	0	0
Related Temperature, Dose 3 [N=260;259;260]	67	34	34
Any Irritability, Dose 3 [N=260;259;260]	138	138	138
Grade 3 Irritability, Dose 3 [N=260;259;260]	19	5	5
Related Irritability, Dose 3 [N=260;259;260]	132	133	133
Any Loss of appetite, Dose 3 [N=260;259;260]	63	59	59
Grade 3 Loss of appetite, Dose 3 [N=260;260;260]	0	0	0
Related Loss of appetite, Dose 3 [N=260;259;260]	58	54	54
Any Drowsiness, Across doses [N=260;260;260]	231	215	215
Grade 3 Drowsiness, Across doses [N=260;260;260]	14	7	7
Related Drowsiness, Across doses [N=260;260;260]	227	213	213
Any Temperature, Across doses [N=260;260;260]	153	110	110
Grade 3 Temperature, Across doses [N=260;260;260]	0	0	0
Related Temperature, Across doses [N=260;260;260]	149	106	106
Any Irritability, Across doses [N=260;260;260]	241	235	235
Grade 3 Irritability, Across doses [N=260;260;260	42	16	16
Related Irritability, Across doses [N=260;260;260]	238	232	232
Any Loss of appetite, Across doses [N=260;260;260]	155	153	153
Grade 3 Loss of appetite, Across doses [N=260;260;	4	1	1
Related Loss of appetite, Across doses [N=260;260;	152	148	148

No statistical analyses for this end point

Secondary: Number of subjects with unsolicited adverse events (AEs) - Primary vaccination

Top of page

End point title

Number of subjects with unsolicited adverse events (AEs) - Primary vaccination

End point description

An AE is 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. “Any” is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

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

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	260	260
Units: Subjects	181	177	185

No statistical analyses for this end point

Secondary: Number of subjects with serious adverse events (SAEs)

Top of page

End point title

Number of subjects with serious adverse events (SAEs)

End point description

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. The Primary Total Vaccinated cohort included all vaccinated subjects who received at least one primary dose.

End point type

Secondary

End point timeframe

Throughout the entire study period (up to Month 21)

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	260	260	260
Units: Subjects
Subject(s) with SAE(s)	35	26	35

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms -Booster vaccination

Top of page

End point title

Number of subjects with solicited local symptoms -Booster vaccination

End point description

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling > 30 millimeters from injection site. The Booster Total Vaccinated cohort included all subjects vaccinated with the booster dose.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following booster dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	257	258	258
Units: Subjects
Any Pain (N=257;258; 258)	174	161	145
Grade 3 Pain (N=257;258; 258)	21	21	7
Any Redness (N=257;258; 258)	175	144	180
Grade 3 Redness (N=257;258; 258)	22	10	10
Any Swelling (N=257;258; 258)	185	146	160
Grade 3 Swelling (N=257;258; 258)	27	15	11

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms - Booster vaccination

Top of page

End point title

Number of subjects with solicited general symptoms - Booster vaccination

End point description

Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. Related symptom was defined as a general symptom assessed by the investigator as causally related to study vaccination. The Booster Total Vaccinated cohort included all subjects vaccinated with the booster dose.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following booster dose

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	256	258	258
Units: Subjects
Any Drowsiness	131	118	128
Grade 3 Drowsiness	6	5	3
Related Drowsiness	126	110	121
Any Temperature	100	100	103
Grade 3 Temperature	1	2	1
Related Temperature	95	89	93
Any Irritability	167	161	166
Grade 3 Irritability	11	8	1
Related Irritability	161	147	159
Any Loss of appetite	93	83	111
Grade 3 Loss of appetite	5	0	2
Related Loss of appetite	89	72	101

No statistical analyses for this end point

Secondary: Number of subjects with unsolicited adverse events (AEs) - Booster vaccination

Top of page

End point title

Number of subjects with unsolicited adverse events (AEs) - Booster vaccination

End point description

An AE is 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. “Any” was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. The Booster Total Vaccinated cohort included all subjects vaccinated with the booster dose.

End point type

Secondary

End point timeframe

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

End point values	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Number of subjects analysed	257	259	258
Units: Subjects	106	105	105

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

xSolicited local and general symptoms: during the 4-day (Days 0-3) post-primary and post-booster vaccination; Unsolicited AEs: during the 31-day (Days 0-30) post-primary and post-booster vaccination; SAEs: during the entire study period (up to Month 21).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

Synflorix + Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix + Pediacel Group

Reporting group description

Reporting group title

Prevenar + Pediacel Group

Reporting group description

Serious adverse events	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Total subjects affected by serious adverse events
subjects affected / exposed	35 / 260 (13.46%)	35 / 260 (13.46%)	26 / 260 (10.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Concussion
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 260 (1.15%)	2 / 260 (0.77%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Greenstick fracture
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Poisoning
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thermal burn
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Haematoma
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Velo-cardio-facial syndrome
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile convulsion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Status epilepticus
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Adhesion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Coeliac disease
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal obstruction
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal stenosis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intussusception
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Apparent life threatening event
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 260 (0.77%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchial hyperreactivity
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 260 (0.77%)	4 / 260 (1.54%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchospasm
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Status asthmaticus
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Hyperhidrosis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 260 (1.15%)	1 / 260 (0.38%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchopneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enterovirus infection
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
alternative assessment type: Non-systematic
subjects affected / exposed	8 / 260 (3.08%)	5 / 260 (1.92%)	4 / 260 (1.54%)
occurrences causally related to treatment / all	0 / 8	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis adenovirus
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis norovirus
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	2 / 260 (0.77%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intervertebral discitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection viral
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mastoiditis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oral herpes
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Otitis media
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 260 (1.15%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	3 / 260 (1.15%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia primary atypical
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	3 / 260 (1.15%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
alternative assessment type: Non-systematic
subjects affected / exposed	5 / 260 (1.92%)	5 / 260 (1.92%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	0 / 260 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 260 (0.38%)	4 / 260 (1.54%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	2 / 260 (0.77%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	1 / 260 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Feeding disorder neonatal
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 260 (0.00%)	0 / 260 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Synflorix + Infanrix hexa Group	Synflorix + Pediacel Group	Prevenar + Pediacel Group
Total subjects affected by non serious adverse events
subjects affected / exposed	260 / 260 (100.00%)	260 / 260 (100.00%)	260 / 260 (100.00%)
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	195 / 260 (75.00%)	179 / 260 (68.85%)	164 / 260 (63.08%)
occurrences all number	364	297	275
Pain
subjects affected / exposed	227 / 260 (87.31%)	219 / 260 (84.23%)	208 / 260 (80.00%)
occurrences all number	573	527	464
Erythema
subjects affected / exposed	231 / 260 (88.85%)	210 / 260 (80.77%)	222 / 260 (85.38%)
occurrences all number	546	528	542
Swelling
subjects affected / exposed	232 / 260 (89.23%)	220 / 260 (84.62%)	211 / 260 (81.15%)
occurrences all number	610	559	516
Somnolence
subjects affected / exposed	240 / 260 (92.31%)	237 / 260 (91.15%)	225 / 260 (86.54%)
occurrences all number	598	544	553
Irritability
subjects affected / exposed	252 / 260 (96.92%)	242 / 260 (93.08%)	247 / 260 (95.00%)
occurrences all number	676	659	649
Decreased appetite
subjects affected / exposed	182 / 260 (70.00%)	174 / 260 (66.92%)	191 / 260 (73.46%)
occurrences all number	326	309	342
Injection site haematoma
subjects affected / exposed	12 / 260 (4.62%)	16 / 260 (6.15%)	7 / 260 (2.69%)
occurrences all number	15	16	8
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	22 / 260 (8.46%)	21 / 260 (8.08%)	15 / 260 (5.77%)
occurrences all number	25	24	17
Vomiting
subjects affected / exposed	10 / 260 (3.85%)	13 / 260 (5.00%)	16 / 260 (6.15%)
occurrences all number	10	14	20
Enteritis
subjects affected / exposed	17 / 260 (6.54%)	8 / 260 (3.08%)	12 / 260 (4.62%)
occurrences all number	17	9	12
Respiratory, thoracic and mediastinal disorders
Wheezing
subjects affected / exposed	19 / 260 (7.31%)	10 / 260 (3.85%)	17 / 260 (6.54%)
occurrences all number	21	11	17
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	25 / 260 (9.62%)	16 / 260 (6.15%)	18 / 260 (6.92%)
occurrences all number	25	17	19
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	117 / 260 (45.00%)	125 / 260 (48.08%)	133 / 260 (51.15%)
occurrences all number	153	160	170
Gastroenteritis
subjects affected / exposed	23 / 260 (8.85%)	17 / 260 (6.54%)	17 / 260 (6.54%)
occurrences all number	24	17	17
Viral infection
alternative assessment type: Non-systematic
subjects affected / exposed	10 / 260 (3.85%)	10 / 260 (3.85%)	24 / 260 (9.23%)
occurrences all number	12	10	24
Otitis media
subjects affected / exposed	22 / 260 (8.46%)	14 / 260 (5.38%)	10 / 260 (3.85%)
occurrences all number	22	14	11

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

22 Nov 2007

A first amendment was made to the protocol in response to comments from the Dutch Authorities to clarify that this study was a single-centre study.

30 Jan 2008

On request of the Dutch Authorities, a second amendment to the protocol was made. Changes concerned the study design: 1) Before vaccination at Visit 1 no blood sample was to be collected; 2) The priority ranking for testing of opsonophagocytic activity (OPA) activity against the 10 pneumococcal vaccine serotypes in case of insufficient blood sample volume was changed; 3) Testing of OPA activity against the 10 pneumococcal vaccine serotypes was to be done for all subjects i.e. all subjects for which the amount of remaining/available serum is sufficient; 4) The sample size was increased.

14 Aug 2008

Changes concerned the study design: 1) To collect information about factors that could potentially influence nasopharyngeal carriage of Streptococcus (S.). pneumoniae and Haemophilus (H.) influenzae, it was planned that the subjects’ parents/ guardian(s) would be asked some questions at Visits 4, 5, 7, 8 and 9; 2) The recruitment period was changed to 9 months.

22 Mar 2010

The following changes were introduced: 1) Due to the H1N1 influenza pandemic, the children were offered H1N1 influenza vaccine as part of a national pandemic prevention plan. Thus, the age range for the booster vaccination visit and subsequent visits was extended; 2) Further details on microbiological testing were included; 3) A second Interim Analysis was added to evaluate carriage (at 3 timepoints) using classical methods for bacterial identification / typing, additional microbiological techniques for H. influenzae/H. haemolyticus discrimination and quantitative molecular techniques for H. influenzae carriage; 4) The back-up contact details for reporting SAEs were updated.

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.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) - Primary vaccination

Primary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) - Primary vaccination

Primary: Antibody concentration against protein D (PD) - Primary vaccination

Primary: Antibody concentration against protein D (PD) - Primary vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Primary vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Primary vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary vaccination

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Primary vaccination

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Primary vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Primary vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Primary vaccination

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Primary vaccination

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Primary vaccination

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Primary vaccination

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Primary vaccination

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Primary vaccination

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Primary vaccination

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Primary vaccination

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Primary vaccination

Secondary: Anti-polio types 1, 2 and 3 titers - Primary vaccination

Secondary: Anti-polio types 1, 2 and 3 titers - Primary vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Booster vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - Booster vaccination

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - Booster vaccination

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - Booster vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster vaccination

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Booster vaccination

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Booster vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Booster vaccination

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Booster vaccination

Secondary: Concentrations of antibodies against protein D (Anti-PD) - Booster vaccination

Secondary: Concentrations of antibodies against protein D (Anti-PD) - Booster vaccination

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Booster vaccination

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Booster vaccination

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Booster vaccination

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Booster vaccination

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Booster vaccination

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Booster vaccination

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Booster vaccination

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Booster vaccination

Secondary: Anti-polio types 1, 2 and 3 titers - Booster vaccination

Secondary: Anti-polio types 1, 2 and 3 titers - Booster vaccination

Secondary: Number of subjects with booster vaccine response against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies - Booster vaccination

Secondary: Number of subjects with booster vaccine response against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies - Booster vaccination

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - 12 months after booster dose

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL - 12 months after booster dose

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - 12 months after booster dose

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) - 12 months after booster dose

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 months after booster dose

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 months after booster dose

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 months after booster dose

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 months after booster dose

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - 12 months after booster dose

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - 12 months after booster dose

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - 12 months after booster dose

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - 12 months after booster dose

Secondary: Concentrations of antibodies against protein D (Anti-PD) - 12 months after booster dose

Secondary: Concentrations of antibodies against protein D (Anti-PD) - 12 months after booster dose

Secondary: Number of subjects with positive cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the nasopharynx - Primary vaccination

Secondary: Number of subjects with positive cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the nasopharynx - Primary vaccination

Secondary: Number of subjects with positive cultures of Streptococcus Pneumoniae vaccine seroptypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) in the nasopharynx - Primary vaccination

Secondary: Number of subjects with positive cultures of Streptococcus Pneumoniae vaccine seroptypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) in the nasopharynx - Primary vaccination

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs - Primary vaccination

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs - Primary vaccination

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae vaccine serotypes (VS), cross-reactive serotypes (CRS) or other serotypes (OS) identified in nasopharyngeal swabs - Primary vaccination